Assessment of ultrasound tomography as a technique for

quantitative tissue characterization

Citation for published version (APA):
Rietsema, J. (1993). Assessment of ultrasound tomography as a technique for quantitative tissue
characterization Eindhoven: Technische Universiteit Eindhoven DOI: 10.6100/IR398895

DOI:
10.6100/IR398895

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Published: 01/01/1993

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ASSESSMENT OF ULTRASOUND TOMOGRAPHY
AS A TECHNIQUE FOR
QUANTITATIVE TISSUE CHARACTERIZATION
CIP-DATA KONINKLIJKE BffiLIOTHEEK, DEN HAAG

Rietsema, Jan

Assessment of ultrasound tomography as a technique for

quantitative tissue characterization I Jan Rietsema. -
[S.l. : s.n.]. - Fig., photos, tab.
Thesis Eindhoven. - With ref. - With summary in Dutch.
ISBN 90-9006207-6
NUGI 743
Subject headings: ultrasound computerised tomography I
ultrasonic propagation I tissue characterization.
ASSESSMENT OF ULTRASOUND TOMOGRAPHY
AS A TECHNIQUE FOR
QUANTITATIVE TISSUE CHARACTERIZATION

PROEFSCHRIFT

ter verkrijging van de graad van doctor aan de

Technische Universiteit Eindhoven, op gezag van
de Rector Magnificus, prof. dr. J .H. van Lint, voor
een conunissie aangewezen door het College
van Dekanen in het openbaar te verdedigen op
vrijdag 9 juli 1993 om 16.00 uur

door
JAN RIETSEMA

geboren te Zwolle
Dit proefschrift is goedgekeurd door de promotoren
prof. dr. ir. J.E.W . Beneken
en
prof. dr. ir. N. Bom

Co-promotor: prof. dr. ir. J.M. Thijssen

Things should be made
as simple as possible,
but no simpler.

-Albert Einstein-
Table of contents

List of symbols viii

List of abbreviations x

I General introduetion 1
Ll Ultrasound tissue characterization 3
1.1.1 Transmission tomography 4
1.1.2 Reflection tomography 6
1.1.3 Quantitative B-mode imaging 7
1.1.4 Other noninvasive tissue characterization techniques 9
1.2 Fundamentals of medica! ultrasound 10
1.3 Scope of this thesis 14

11 Measurement techniques and measurement device 16

11.1 Principles of computerized tomography 16
11.2 Measurement device 19
11.3 Measurement of the acoustic parameters 20
11.3.1 Speed of sound 20
11.3.2 Attenuation coefficient 22
11.3.3 Attenuation slope 24
11.3.4 Reflectivity 26
11.4 Reconstruction principles 28
11.4.1 Filtered backprojection algorithm 30
11.4.2 Direct Fourier inversion algorithm 31
11.4.3 Hartley transform in image reconstruction 32

Ill Assessment of the backscatter measurement 35

ill.l Theoretica! foundation 35
m.2 Implementation 40
111.3 Experiments 41
III.4 Discussion 45

IV Assessment of the performance of the tomograph 47

IV.1 Measurements on phantoms 47
IV.l.l Tissue-mimicking phantoms 47
IV.1.2 Standard measurement protocol for phantom studies 49
JV.2 Phantom study on spatial resolution 50
IV.2.1 Introduetion 50
JV.2.2 Results 52

VI
IV.2.3 Discussion 53
IV.3 Phantom study on contrast resolution 54
IV.3.1 Introduetion 54
IV.3.2 Results 55
IV.3.3 Discussion 56
IV.4 Phantom study on quantitative accuracy 56
IV.4.1 Quantitative characterization using an acoustic
macroscope 57
IV.4.2 Relationship between size and quantitative accuracy 64
IV.5 Dominant sourees of artifacts influencing the image quality 66
IV.5.1 Refraction 66
IV.5.2 Interference and phase cancellation 70
IV.6 General Discussion 79

V Imaging bone-containing tissue structures 80

V.1 Measurements on a 'bone phantom' 81
V.l.l Method 81
V.1.2 Results 83
V.1.3 Discussion 85
V.2 Current measurement techniques for osteoporosis 87
V.2.1 Osteoporosis 87
V.2.2 Diagnostic techniques 88
V.2.3 Ultrasonic assessment of bone 90
V.3 Ultrasound tomography measurements on bone in vitro 91
V.4 In vivo measurements of human extremities 94
V.5 Conclusion 97

VI Clinical perspective of ultrasound tomography 99

VI.l Tissue classification using acoustic parameters 99
VI.2 Clinical applicability of ultrasound tomögràphy 101
Vl.3 Recommendations 104
Vl.4 General conclusion 105

References 106

Summary 123

Samenvatting 128

Nawoord 133

Curriculum vitae 134

VIl
List of symbols

a a radius (e.g. of a scatterer)

b a constant
c speed of sound
d thickness
f frequency
f(x,y) a two-dimensional function
g(v) a filter function
k wave number (=27t/À)
Pe(v) projection at angle e
r a ra<lius
time
x distance, depth
x,y cartesian coordinates
v,w rotated cartesian coordinates
A signa! amplitude
BIA nonlinearity parameter
E elastic modulus
F(X,Y) Fourier transfarm of f(x,y)
F(R,<I>) Fourier transfarm in polar coor<linates
y Fourier transfarm operator
H(X,Y) Hartley transfarm of f(x,y)
I signa! intensity
M an integer
N an integer
P(r,t) pressure in the acoustic wave
Q(r,t) scattering strength of a medium
R reflection coefficient
uP block pulse with the duration equal to half the period time of
the received ultrasound pulse
V voltage, volume
w signa! power
z acoustic impedance
a amplitude attenuation coefficient
ö Dirac delta function
1( compressibility
À wavelength
!l intensity (or power) attenuation coefficient
llbs backscattering coefficient
p density of a medium
(J2 varianee of a Gaussian amplitude spectrum
a

viii
effective scattering cross-section
width of ultrasound pulse
angular frequency (=2nf)
small tluctuation
an angle
an angle
convolution
differential operator
Laplacian operator

ix
List of abbreviations

2-D two dimensional

AID analog to digital
A-mode amplitude mode
B-mode brightness mode
BUA broadband ultrasound attenuation
C-D diagram contrast detail visibility diagram
DC direct current
DHT discrete Hartley transfarm
DPA dual photon absorptiometry
DXA dual-energy X-ray absorptiometry
EIT electrical impedance tomography
EPC echo pulse counts, number of transmitted pulses for one echo
sample
FFT fast Fourier transfarm
FHT fast Hartley transfarm
FT Fourier transfarm
HT Hartley transfarm
m integrated backscatter
MRI magnetic resonance imaging
MRS magnetic resonance spectroscopy
MTF modulation transfer function
NDT non-destructive testing
PET positron emission tomography
PMMA polymethylmethacrylate
QCT quantitative computerized tomography
RF radio-frequency
ROl region of interest
SAM scanning acoustic microscopy
SLAM scanned laser acoustic microscopy
SPA single photon absorptiometry
SPECT single photon emission computerized tomography
TGC time gain compensation
TOF time of flight
TPC TOF pulse counts, number of reverberation cycles
TIS TOF time scaler
XCT X-ray computerized tomography

x
I General introduetion

Ultrasound techniques are widely used as diagnostic techniques in any modern hospita!.
Ultrasound is the first diagnostic technique to be used for a great majority of the patients
and often it wiJl even be the only one used. Ultrasound is used in almost all medica!
specialisms. Generally known are the pictures of unborn children made by B-mode
echography. On a worldwide basis ultrasound covers nearly 25% of all imaging studies
perfonned (Leopold, 1991). Of great importance for the popularity of ultrasound is the fact
that it is considered to be harmless for biologica! tissue, at least in the intensity range used
in medica! applications.
Besides the above-mentioned imaging techniques, ultrasound is also used for flow
measurements. In the last few years these so-called Doppier techniques have gained in
importance by the development of the colour Doppier technique (Evans et al., 1989).

The fust diagnostic application of ultrasound was reported by Dussik (1942; Dussik et al.,
1947). He described a transmission technique to produce images of the head. A similar
scanner was constructed by Ballantine and co-workers (1950; Hueter and Bolt, 1951). In
the first instanee the results seemed to be very promising. It was assumed that the images
depicted intracerebral structures, particulary the geometry of the ventri cles of the brain and
the technique was meant to be used in the detection of brain tumours. In later publications
(Güttner et al., 1952; Ballantine et al., 1954) it was proved that these images of the head
did not contain any clinical infonnation about the brain, but that only artifacts were
imaged.
In the meantime, stimulated by new transducer technologies, a pulse-echo technique
was developed for non-destructive material testing (NDT). The first clinical pulse-echo
application was detecting gallstones by means of such a NDT apparatus (Ludwig and
Struthers, 1950). In the following decades the pulse-echo techniques developed rapidly and
nowadays applications can be found in various fields of medica) diagnostics. Results are
publisbed in leading journals, for instanee the 'Journal of Clinical Ultrasound' .
In spite of the discouraging results, developments continued on transmission ultrasound
systems. To record the transmitted beam, research was done on ultrasound image
converters. The sound pattem converted into a corresponding voltage by a piezoelectric
plate produces a visible image, by use of relevision scanning techniques (Smyth et al.,
1963; Jacobs, 1965). This idea of the ultrasound camera was improved by Green et al.
(1974). By use of a system of acoustic lenses the sound field was scanned past a linear
array of receiving elements. The quality of the in vivo images was degraded by artifacts
due to refraction, reflection and diffraction.
The Doppier technology also started with a transmission mode (Baldes et al., 1957) but
soon the development switched to the reileetion mode (Satomura, 1957). After a short
period the Doppier technique was used for clinical applications. The Doppier method shall
not be mentioned further in this thesis, because it is outside its scope.
In the field of the transmission techniques, acoustic microscopy has to be mentioned.
This technique uses frequencies in the gigahertz range to produce extremely high resolution
images of the acoustic properties of tissue samples. In 1949 the first artiele on acoustic
microscopy appeared (Sokolov, 1949). The further development of this technique started
only in 1959 with a publication about ultrasonic absorption microscopy (Dunn and Frey,
1959). Korpel and co-workers (1971) combined acoustic mîcroscopy with laser technology
into a Scanned Laser Acoustic Microscope (SLAM). In 1974 Lemons and Quate (1974,
1975) described a technique in which a tissue sample mounted on a plastic film is scanned
with a highly focused (by sapphire lenses) ultrasonic beam. This technique is called
Scanning Acoustic Microscopy (SAM). Acoustic microscopy is not practicabie as a
noninvasive technique but may be very useful in the field of histopathology.
A new ultrasonic imaging method called time delay speetrometry was proposed in 1974
(Heyser and Le Croisette, 1974). This technique involves the transmission of an ultrasound
beam with a repetitive linear frequency sweep through the object under investigation. The
transmitted frequency is a linear function of time and therefore the difference between the
transmitted and received frequencies is constantfora given transit time. The signals that
do not arrive by a straight path could be separated from those that are of interest. A time-
of-flight image and an absorption image could be produced with this technique. The
method was never developed for clinical application, however.
In the early seventies Greenleaf and co-workers (1974, 1975) developed the
transmission ultrasound computerized tomography. This technique appears to be very
useful for quantitative tissue characterization. The bistorical perspective of transmission
tomography wil! be discussed in detail in the next section (1.1.1 ).

After this short survey of the history of transmission techniques in diagnostic ultrasound,
the next section will place emphasis on ultrasound tissue characterization. Transmission
tomography, reflection tomography and quantitative B-mode imaging wil! be discussed.
Developed methods and publisbed results will be summarized. Because of a growing
interest in tissue characterization more techniques are developed outside the range of
ultrasound. At the end of that section these methods for tissue characterization will be
mentioned.
To understand the complex interactions between ultrasound and biologica! tissue it is
essential to know more about the physics of ultrasound. The second section deals with the
fundamentals of medica] ultrasound. This chapter will conclude with a description of the
aim and an outlîne of the thesis.

2
1.1 Ultrasound tissue characterization

Current clinical ultrasound imaging systems produce qualitative images of tissue interfaces
and scattering and although distances between interfaces may be relatively accurate,
quantitative evaluation of fundamentál acoustic properties is not possible. The latter is the
field of quantitative tissue characterization. Tissue characterization was defined by Chivers
( 1981) as the identification of one or more physical parameters of a small volume of tissue
that are sufficiently well correlated with the type or condition of the tissue that the
measurement of these physical parameters may alone be used as an effective index of the
type or condition of that volume of tissue. The present section describes ultrasound tissue
characterization techniques in detail and at the end other tissue characterization techniques
will be considered briefly.
As a result of a large number of studies the acoustic properties in various types of
mammalian tissue are known (Chivers and Parry, 1978; Gosset al., 1978, 1980). Table I.1
presents typical values of acoustic properties in various types of human tissue. The
objective is to gain an impression of the range of the values. The experimental data are
dependent among other things on the condition of the tissue, the temperature, the
measurement method and the frequency used. The diversity in purpose of measurements
makes it difficult to compare the reported data.

tissue type speed of sound attenuation

(mis) coefficient*(dB/cm)

skull bone . 2770 . 13

............................................................................................................................................................................................
. ..
•••~~~•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••oo•~•~!~•••••••••••••••••••••••loo•••••••••••••••••••••••~ o~oooooo•••••••••••••••••••
..

: :~ :.":l~: (: '~ ~: =: J,:): : : :·: : :J: : : : : : : :l: :l;~i.:.~: : : : : : : :t: : : : : : : : : ' :~:~: : :~: : : : : : : :
kidney l 1570 i 0.8 (1.5)
...;·~~:;····························································,························~-~~~······················t··················~·:~·-~·;·:;·;···················
···~~~~···~~·~;~~:;~·~:;······························r······················~·~;~······················r·······················~·:~·························

Table 1.1: Typical values of acoustic properties in various types of human tissue as mentioned in
the literature. Souree of data: Goss et al., 1978.
• Values measured at I MHz unless other frequency mentioned between brackets (in MHz).

The range of values of the speed of sound in normal and pathological tissues within one
specific organ are presented in table 1.2. The breast was chosen because the data was
readily available and the nature of the internal tissues vary. This compilation show that
large standard deviations and small differences between various breast tissues are noted.

3
 tissue type I speed of sound (mis)

subcutaneous fat 1350-1487

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . uooooooo . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

parenchyma 1445-1609
.......................................................................................................................................
fibroadenoma 1540-1582
........................................................................................................................................
benign solid 1514-1576
......................................................................................................................................
cyst
···~~·~~;~~:~ . . . . . . . . . . . . . . . .r. . . . . . 1500-1578
~·~·~~·~·~·~~·~···················

Table 1.2: The range of values of speed of sound in various breast

tissues as mentioned in the literature. Sourees of data: Glover, 1977;
Greenleaf and Bahn, 1981; Scherzinger et al., 1989.

1.1.1 Transmission tomography

As a result of a series of publications on the algorithms to obtain a cross-sectional image

of the distribution of a physical quantity in an object from a set of one-dimensional data
(projections), Greenleaf and co-workers (1974, 1975) introduced the principles of
transmission ultrasound computerized tomography.
Radon (1917) was the first to treat the relationship between a two-dimensional function
and the set of projections. At that time, there was no reason for stating and solving this
problem other than that it was a very interesting mathematica! problem and a challenge to
solve it. In 1954 Braceweil (Bracewell and Roberts, 1954; Bracewell, 1956) was the first
to present a practical application of the inverse Radon transfonn. He applied the
mathematica! theory in radio-astronomy mapping solar microwave activity from a series
of strip detector signals. The first known application to biology was made by De Rosier
and Klug (1968) who obtained the cross-sectional structure of the tail of a bacteriophage
from projections obiained with an electron microscope.
In 1971 the principle of image reconstruction from projections was commercially
introduced into medica! radiology by Hounsfield of EMI Ltd. (1972, 1973), who produced
a clinically useful machine specifically for imaging the inside of the head. The technique
was immediately seen to be useful and the development of X-ray computerized
tomography is progressing by storm. Nowadays the X-ray CT scanner is almost a basic
device in every fair-sized hospita! in the western world.
As already stated, shortly after the development of X-ray computerized tomography,
Greenleaf and co-workers presented the transmission ultrasound computerized tomography.
They showed the reconstructibility of the two-dimensional distribution of the attenuation
and the speed of sound (Greenleaf et al., 1974, 1975). The objective of ultrasound
tomography is to obtain parametrie images of quantitative values of material properties for
evaluating the state of tissue.

4
 The acoustic tissue properties under study are the speed of sound and the attenuation.
Speed of sound or refractive index imaging is done by measuring the time of flight from
a sound pulse (Greenleaf et al., 1975; Glover and Sharp, 1977). Two main techniques have
been described to measure the attenuation. The first metbod compares the total energies
of the received and transmitted ultrasonic waveforms (Greenleaf et al., 1974). The second
metbod is based on the idea of using the frequency shifts for estimating the attenuation
(Dines and Kak, 1979).
In vitro studies were publisbed as well as results of in vivo clinical studies. The main
clinical application is the detection and classification of tumours in the female breast
(Glover and Sharp, 1977; Glover, 1977; Carson et al., 1978; Greenleaf et al., 1978; Carson
et al., 1981; Greenleaf and Bahn, 1981; Schreiman et al., 1984; Scherzinger, et al., 1989).
The speed of sound as well as the attenuation for various breast tissues were considered.
Simultaneous measurements of these properties were made across sequentia! corona! planes
of the breast. The studies were performed with a small number of patients. The findings
of all studies are an increased speed of sound in breast cancer tissue. The attenuation
information is used as a supplement in èharacterizing various types of breast tissue.
Although all studies mentioned problems with the resolution and accuracy of the
reconstructions, the method is considered a potentially useful diagnostic technique.
The in vitro studies contain an evaluation of structures containing bone (Carson et al.,
1977). Carson showed the possibility of imaging the attenuation properties of a leg of lamb
containing bone. Dines and co-workers (1981) reported successful imaging ofthe brain in
an intact human head. Applications of testiele imaging were also described (Hiller and
Ermert, 1981 ). For the investigation of the relation between cardiac function and
corresponding changes in cardiac geometry, ultrasound computerized tomography using the
speed of sound was used by Mol (1981 ). Transmission ultrasound tomography also can be
used to study in vitro the distribution of myocardial ischaemia (Chandrasekaran et al.,
1986). This study indicated that ischaemie regions are associated with increased
backscatter, decreased attenuation and decreased speed of sound.
The above-mentioned methods all use the assumption that sound behaves analogously
to geometrical opties where the energy is assumed to propagate along rays. Another
approach is called diffraction tomography (Iwata and Nagata, 1974; Mueller et al., 1979;
Mueller, 1980; Kaveh et al., 1981, 1982; Devaney, 1982; Sponheim et al., 1991). This is
an actvaneed technique in which a wave equation is used as a descriptor of wave
propagation rather than a simple straight ray model. The name diffraction tomography was
chosen because of the relatively large wavelengtbs associated with typical ultrasonic
sources, which result in diffraction of the sound wave when it propagates through the
object to be scanned. Using special reconstruction algorithms within the so-called Rytov
or Born approximations this metbod is also capable of giving quantitati ve images of the
speed of sound and the absorption. This thesis only deals with the straight ray
reconstruction tomography and will not go further into diffraction techniques. The principle
of the straight ray reconstruction tomography wil! be described in chapter 11.
In spite of the above results ultrasound computerized tomography bas not yet gained
wide acceptance in clinical practice. Two main reasons account for this . First, the
complexity and costof the systems used and the resulting poor quality of the images. This
quality is influenced by artifacts due to reflection, refraction and diffraction. Many studies

5
have been perfonned on artifact reduction in computerized tomography (Klepper et al.,
1977; Schmitt et al., 1984b; Fitting et al., 1984). The iniluence of the artifacts on the
image quality will be extensively discussed in this thesis.
In the second place it is not yet clear whether ultrasound computerized tomography can
compete with or complement existing medica) imaging systems. In the case of breast
imaging it is not yet clear whether ultrasound computerized tomography is able to replace
or complete the X-ray mammography as a screening or as a diagnosing technique.

1.1.2 Reneetion tomography

Ultrasound tomography is not restricted to systems using transmission of the ultrasound

beam. Ultrasound tomography in the reileetion mode has also been described. Reileetion
ultrasound computerized tomography images the ultrasonic reilectivity in a medium.
Several groups (Wade et al., 1978; Johnson et al., 1978) described methods to make a
reconstruction of the reflectivity based on the principle that the received echoes from
scatterers at the same range are integrated over the transducer and that the echoes from
greater ranges are received at later times. So, a point on an A-mode like trace can be
interpreled as the line integral of the echoes over a circular are and the received echo train
can be considered a projection. A set of these projections can be reconstructed using the
conventional reconstruction algorithms. These methods make use of fan beam scanning to
obtain the reflected data.
In 1979 a comprehensive theoretica] analysis waspresentedof the problem of using
echo data to reconstruct an image of the acoustic reflectivity for the case of a circular
transducer array and a circular integration path (Norton and Linzer, 1979a). The
assumptions to make a traetabie analysis are that the medium is weakly reflecting, the
speed of sound is constant and the absorption is uniform. Additionally the medium is
assumed to contain isolated point scatterers without mutual interactions. Computer
simulations are perfonned to support the theory. Dines and Goss (1987) refined this model
in the sense that they account for the practical effects of beam pattem and backscatter
di vergence.
Norton and Linzer (1979b) also handled the problem of three-dimensional image
reconstruction from echo data from the point of view of conventional tomography. They
started with the assumption that the backscattered signals provided measurements of
surface integrals of a postulated reflectivity function and then applied standard
reconstruction concepts, such as backprojection. This direct approach is potentially superior
to staclcing multiple transducer sections. Later they solved this problem as an inverse
scattering problem (1981).
Ex perimental results of ultrasound reileetion tomography that are very promising were
publisbed by Hiller and Ennert (1980, 1981). They make use of animaging system that
uses a linear transducer array and special data processing to reconstruct echo data in a
tomographic manner. By analogy with the above-described methods, each B-mode image
is integrated over the aperture axis for each point of the time axis. These 'pseudo-
projections' are reconstructed. This approach is based upon a plane wave approximation
instead of a spherical wave interrogating the object as mentioned before.

6
 Another processing method, applied by the same authors, convolves each B-mode
image with a filter function and then all filtered images are superimposed to give the final
image. This alternative approach is called computer-aided compound scanning. In the
reflection mode one transducer picks up a number of conventional B-scans. Computerized
superposition of all single B-mode images eliminates the poor lateral resolution and makes
use of the good axial resolution for all directions. However, a simple summation leads to
a blurred image. An algorithm analogous to the conventional filtered backprojection
algorithm is therefore necessary to obtain a high quality image from reflectior6 ultrasound
tomography. A system analysis of these methods was presented in 1984 (Hiller and
Ermert, 1984).
Experimental results were also published by Maderlechner et al. (1980). They reported
results of experiments on several objects and excised organs and the influence of several
physical effects on image quality in the procedure of reflection ultrasound tomography in
the same two modes as Hiller and Ermert (1980).
After some more in vivo experiments the clinical applications were considered. Hiller
and Ermert (1982) described the medica! applications of transmission ultrasound
tomography and reflection ultrasound tomography. They considered only organs that can
be viewed from 360 ·, so both modes can be applied. lt appears that ultrasound
tomography is not useful for imaging the whole human body, but it is suitable for imaging
smal! organs such as the breast and testicles. Röhrlein and Ermert (1985) investigated the
possibilities of using the computerized compound scan technique with a limited angle area.
This gives the possibility of imaging organs which do not allow a 360 • imaging range.
Reflection ultrasound tomography works exactly if the speed of sound is constant in
the whole imaged cross-section. The speed of sound image and the absorption image,
obtained with transmission ultrasound tomography, could be used to correct the reflection
mode image. Experimental results show that it is possible to avoid distortions in the
reconstructions due tospeedof sound differences (Greenleaf et al., 1977; J(jm et al., 1984;
Bartelt 1988; Jago and Whittingham, 1991).
A new developed diffraction tomography algorithm in the retlection mode was
described by Roberts and Kak (1985). This algorithm makes use of a very simple scanning
geometry and combined with speetral extrapolation techniques makes possible a
reconstruction of objects for which the Born approximation holds.
In the next subsection another tissue characterization technique, quantitative B-mode
imaging, will be discussed.

1.1.3 Quantitative B-mode imaging

In conventional B-mode images the amplitude of the received echo signals is displayed.
In these B-mode images trained observers can detect large-scale structures.
A few years ago it became clear that the full diagnostic information contained in B-mode
images is not accessible by simply viewing the image. This prompted research on methods
to obtain more objective, more quantitative images. Quantitative methods are used to make
estimates of the acoustic properties of tissue that relate with the condition or state of the
tissue, or to characterize the image texture.

7
 To obtain objective, quantitative images it is necessary to be independent of the device
and the operator. To be able to make reproducible images, pre-processing has to be done
before analysis of the signals. This pre-processing corrects for the acoustic beam
characteristics that induce a depth dependence. In case of a time-gain compensation (TGC),
a recompensation has to be done.
The acoustic properties under study are the attenuation, the backscattering, the speed
of sound and the nonlinearity parameter B/A. The latter parameter is not obtained from the
backscattered signa!, but it appears to be a useful parameter in quantitative ultrasound
tissue characterization. For this reason it will be mentioned in this section. By applying a
multi-parameter method, the possibilities of tissue characterization are improved. In spite
of the large amount of research, no method is routinely employed in clinical practice.
Different methods are developed to obtain quantitative information about the
attenuation coefficient of tissue. One method converts the RF-signals from various depths
to power spectra. The log power spectra from two different depths are subtracted from
each other and a power law line is fitted to the result. This method is called the speetral
difference method (Kuc, 1980). Because attenuation in soft tissue is described by a power
law function of the frequency, this method gives the frequency dependent attenuation
coefficient and the power law dependency. Another method is based on the frequency
dependenee of the attenuation coefficient. The higher frequencies are more attenuated than
the lower ones. The centre frequency of the spectrum plotted versus depth is used to
estimate the attenuation coefficient (Dines and Kak, 1979). For reasons of simplicity
several methods are developed that make use of the measured amplitudes rather than
speetral parameters (Taylor et al., 1986; Garra et al., 1987).
In vivo measurements are obtained for several organs. However, most of the clinical
studies are concerned with measurements in the liver. Although the results show a large
variability, it appears that the attenuation coefficient has some ability to separate normal
from diseased tissues (Taylor et al., 1986).
The backscatter coefficient appears to correlate with pathologies. Quantitative
information about the scattering in the form of the backscatter coefficient of the medium,
determined by size, concentration, strength and shape of the scatterers, is obtained by
analysing the corrected backscattered power spectrum (Lizzi et al., 1983; Madsen et al.,
1984; Lizzi et al., 1986; Romijn et al., 1989a, 1989b).
In vivo measurements of the speed of sound create great difficulties. Nevertheless,
many methods have been proposed to estimate the velocity by means of backscattered
signals. Robinson (1982) described a method in which two images are built up from
different directions. From the displacement in these images of a specific scattering
structure a sound velocity was calculated. Ophir proposed the so called 'beam tracking
method' (1986). The complexity of these methods and the disappointing accuracy decrease
researchers' interest.
The nonlinearity parameter B/A is a measure of the nonlinearity of the pressure-density
relation for a medium. This relation describes the distartion within the waveform, due to
variations of the speed. These variations occur because the density of the medium changes
with pressure. Because the parameter B/A is a property of the medium, it may provide
diagnostic information (Muir and Carstensen, 1980; Law et al., 1985; Errabolu et al.,
1988). The early B/A images of biologica1 tissue were obtained by Ichida et al. (1983).

8
This method is based on measuring the phase shift by interaction of two ultrasonic waves
with different frequencies and power levels. Later on, improved methods to determine the
non-linear parameter B/A of biologica] media were proposed basedon estimating the shift
in phase and frequency (Sehgal et al., 1984; Kim et al., 1990).

The image texture in B-mode images can be characterized as coherent speckle. It is due
to the interaction of ultrasound and the tissue and therefore it can be used as a parameter
for tissue characterization. The quantitative characteristics of texture depend not only on
the tissue but also on the equipment, including the transducer. A correction has to be
applied prior to the analysis, to increase the reproducibility.
The texture of B-mode images can be analysed by first orderand second order statistics
using stochastic signa! analysis (Wagner et al., 1983). First order statistics characterize the
histogram of the echo amplitudes. This histogram is quantified by its mean and the
standard deviation. Many other features can be extracted from the first order grey level
histogram. The second order statistics are characterized by the autocovariance function.
The full width at half maximum of this function is an estimate of the average size of the
speckle.
Speckle analysis can be used for diagnostic purposes. In a clinical study performed by
Oosterveld et al. (1991) it was shown, for instanee that the first order statistica! parameters
could differentiate between several kinds of liver pathology.

1.1.4 Other noninvasive tissue characterization techniques

Magnetic resonance imaging (MRI) is a relatively new imaging technique (Lauterbur,

1973). The contrast on the MR images is basically the result of the relaxation times Tl and
T2 and the proton density. Tl is the characteristic time of the process of returning to a
state of equilibrium from an excited state following the impulse given by a radio-frequency
burst. T2 characterizes the dephasing of spins. The proton density reflects the water
content. Because of its high soft tissue contrast it was expected that MRI might be used
fortissue characterization. lt was claimed that quantitative measurements of relaxation time
could be used as a diagnostic technique for noninvasive tissue characterization (Damadian,
1971). Later this claim was refuted because in vivo relaxation time measurements show
great variability (Rinck, 1985; Bottomley et al., 1987). Increase of measurement accuracies
change the perspective. There are some successful applications of relaxation time
measurements for tissue characterization. For instanee the differential diagnosis of
leukaemie bone marrow could be made by relaxation time measurements (lensen et al.,
1990; Thomsen et al., 1987). In cirrhosis, also, a prolonged Tl relaxation time is found
(Thomsen et al., 1990).
A spectroscopie approach to magnetic resonance (MRS) is also possible and this is
widely used in chemica) and biochemica! research. The spectra are formed by the effect
that not all protons exhibit the same frequency when submitted to the same external
magnetic field. The higher the field strength, the better the spectra will be. Based on such
spectra it becomes possible to analyse the chemica! composition of tissue samples. lt is
still unclear whether the combination of MRI and MRS may improve the specificity of

9
tissue characterization by magnetic resonance techniques.
As far as known at this moment MRI and MRS are harmless methods for the patients.
A limitation of MR measurements is that the equipment is immobile and generally more
expensive than other imaging techniques and the examination time is relatively long.
The examination time for X-ray computerized tomography (XCT) is much shorter.
XCT measures very accurately the attenuation of X-rays passing through an object. The
calculated CT number is related to the linear attenuation coefficient of the material for the
effective energy of the X-ray beam. Since linear attenuation coefficients for soft tissue are
a direct reflection of volume electron densities and of mass densities, the potential exists
to characterize soft tissues by their CT numbers.
Quantitative computerized tomography also offers the possibility of characterizing bone
tissue (Ruegsegger et al., 1976; Genant and Boyd, 1977). By simultaneous measurement
of a calibration phantom, the bone mineral density can be predicted. A disadvantage of X-
ray CT is the use of ionising radiation.
The last technique mentioned in this section is positron emission tomography (PET).
Since the position of a positron emitting radioisotope can be determined by the two
annihilation photons, which are emitted 180 • from one another, detectors positioned
around a patient can determine the line along which the disintegration occurs. PET is an
indirect techni<jue. With a labelled tracer, the metabolism in a variety of organs can be
studied. From the metabolic information characteristics of the tissue can be identified.
Several studies have demonstrated the ability of PET to quantitatively evaluate metabolic
function (Phelps et al., 1986).

1.2 Fundamentals of medica) ultrasound

Ultrasound is a mechanica! wave with a frequency that is too high for perception by the
human auditory system. For this reason, it took until the end of the nineteenth century
before ultrasound was investigated. The lower limit for ultrasound is often taken rather
arbitrarily as 20 kHz. This section briefly describes the physics of ultrasound as far as
applied in this thesis. A thoroughly study of the physics of medical ultrasonics was
published e.g. by Hili (1986).
An ultrasound wave is attenuated, primarily due to absorption and scattering, when it
passes through a medium, such as tissue. Absorption is mainly due to relaxation
phenomena of biologica! macromolecules (Wells, 1975). Tissue exhibits scattering from
histological features such as clusters of cells, small vascular channels and microscopie
calcific aggregations.
Scattering of ultrasound by a partiele greatly depends on the ratio of the size of the
partiele to the wavelengthof the ultrasound wave. A measure for this ratio is the scattering
parameter ka, where k is the wave number and a is the dimension of the particle. Two
scattering regimes are of interest. If ka > 1 the scattering is called geometrie scattering.
This is determined by the laws of reflection and refraction and will be explained later in
this section. If ka< 1 the scattering is called Rayleigh scattering after Lord Rayleigh, who
first studied this theory in 1871. Rayleigh scattering is proportional to the fourth power of

10
frequency and is omnidirectional.
Quantitative measurements of scattering strength would be significant for tissue
characterization. The scattering strength can be measured quantitatively in terms of a
backscattering coefficient.
The propagation of ultrasound, if absorption effects are negiected, is described by a
wave equation, formulated by Morse and lnghard (1968):

where 2.c - VPoKo·

P(r,t) is the sound pressure, ~p(r) and ~IC(r) show the small regional variations in density
and compressibility around mean values Po and Ko· respectively, assuming slight
inhomogeneity.
The most important simplification to solve this general equation is the Born
approximation: the pressure of the sound field can be taken equal to the incident pressure
(P;) if it would travel through a homogeneous medium and only tirst-order scatter will be
considered. The latter assumption means that . the contri bution of each scatterer to the
scattered signa) can then be treated independently, and the resulting scattered signa!
represented as a sum of the contributions from all individual scatterers. The solution is
(Ueda and Ichikawa, 1981; Hili, 1986)

P(r,t) - P;(r,t) + Ps<r,t), (1.2)

where Plr,t) is the scattered wave from the volume V.

1
P s (r,t) _ JQ(r,t)Ö(t-lr -rl!c) d v, (1.3)
v (41t Ir - r 1 1)
where r' is a position vector. Q(r,t) is a scattering strength of a medium:

(1.4)

The first term expresses the contribution of the compressibility fluctuations and the second
term expresses the contribution of the density variations.
A measure of the contribution of scattering to the attenuation is the effective scattering
cross-section, which is defined as the ratio of the total scattered power to the intensity of
the incident wave:

(1.5)

Of particular interest is the backscattering cross-section, which is the ratio of the power

11
scattered back into unit solid angle, located at 180 ' to the direction of the incident
ultrasound.
If the scatterers are randomly positioned and the volume contains sufficient scatterers,
the power scattered will be proportional to the volume of the media and the scattering is
tenned incoherent. In case of incoherent scattering, the scattering strength can be measured
quantitatively in tenns of a backscattering coefficient (!lbs), which is defined as the
backscattering cross-section per unit volume.

In the special case of the inhomogeneities being large with respect to the wavelength, the
scattering response is quite different from the response from a point-like scatterer. At the
interface between two media with different acoustic impedances two phenomena occur:
reflection and refraction. This is illustrated in tigure l.I.

Figure 1.2: Behaviour of ultrasound at the boundary between

two media with different acoustic impedances.

Reflection follows the law that stipulates that the angle of incidence (e;) equals the angle
of reflection (er). The reflected ray also lies in the plane of incidence and on the opposite
site of the nonna!. The plane of incidence is the plane that contains the ray of incidence
and the normaL
Refraction follows Snell's Law that states that the ratio of the sine of the angle of
incidence and the sine of the angle of refraction (e1) equals the ratio of the speed of sound
in the two media:

sine;
(1.6)
sine 1
The energy of the incident wave is shared between the waves reflected and transmitted at
the boundery. The intensity of reflectivity (1/I;) is:

Ir - [z2 cos ei - ZJ cos eI J. (1.7)

I; ~cose; + Z1 cose 1

12
where Z; is the acoustic impedance of a medium (Z; = P;c;). The intensity of
transmissivity is:

4Z1 Z2 cos8;cos8 1
(1.8)
(~cos ei+ zl cos ei
Absorption together with scattering wil! cause attenuation. The attenuation causes an
exponential decrease of the power of the wave as a function of the depth (x):

(1.9)

where J.l is the attenuation coefficient, expressed in termsof nepers (Np) per unit distance.
For many purposes it is more convenient to express the amplitude attenuation coefficient
(<X) as the ratio of signa! amplitudes in decibels per centimetre. The attenuation m
biologica! tissue is frequency dependent (Pohlman, 1939; Hueter 1948; Wells, 1975):

(1.10)

In biologica! tissue the value of the frequency power n is in general between 1 and 2 (Hili,
1978). Frequency dependent attenuation implies the presence of dispersion (Gurumurthy
and Arthur, 1982). This is established by the Kramers-Kronig relations (Kak and Dines,
1978; O'Donnell et al., 1978, 1981).
If tissue exhibits dispersion, the spectrum changes when the pulse passes through the
tissue. It has been shown that a Gaussian modulated pulse remains Gaussian when it passes
through a dispersive medium, such as biologica! tissue (Ferrari and Jones, 1985).
The ultrasound pulse generated by a common piezoelectric transducer is mostly
assumed to have a Gaussian envelope (Dines and Kak, 1979). A Gaussian modulated pulse
has a Gaussian shaped spectrum in the frequency domain. This is also the case for the
transducers used in the experiments describ~ in this thesis. A typical sound pulse from
the transducer used is shown together with its spectrum and the best fitting Gaussian
envelopes in figure 1.2.
Diffraction is the term used to describe the spreading out of a wave in space. The
shape of the sound field depends highly on the source. The sound field generated by an
unfocused ultrasound transducer can basically be divided into the cylindrical near field or
Presnel region and the cone shaped far field or Frauenhofer region. Focusing is achieved
by using an acoustic lens incorporated in the transducer or by using a concave piezoelectric
element. For both options the focus length is fixed .

13
 1.00 I
1.00
I

w
0 0.75 a: 0.75
:::1 w
1-
::i ~
11. 0
:::E 11.
< 0
w
0 0.50 N 0.50
w ::i
N
::i <
< :::E
:::E a:
a: 0
0 0.25 z 0.25
z

0.00 0.00
0 2 0 2 4 8 8 10

TIME (111) FREOUENCY (MHz)

Figure 1.2: Waveform (left) and spectrum (right) of a characteristic ultrasound pulse and the best
fitting Gaussian envelopes.

1.3 Scope of this thesis

This study is a continuation of the research done by Stapper and Sollie (Stapper and Soli ie,
1985; Sollie, 1988). Sollie concluded his doctoral dissertation (1988) with the thesis that
it is possible to build a transmission ultrasound tomograph using cheap and unsophisticated
electronic components and computer equipment. This tomograph rnight be used clinically
as an imaging system. It was his expectation that the system would offer the possibility
of performing a limited degree of tissue characterization.
The aim of the present study is to extend the prototype ultrasound tomograph with a
measurement of the backscattered signal. This measurement has to be performed
simultaneously with the three already existing measurements. Because of the simplicity of
the set-up it is being tried to find unsophisticated electronic components to implement the
measurement and to use only the personal computer available in the set-up. An
experimental evaluation of the imaging characteristics of the system will be performed to
investigate whether the system can be used for quantitative tissue characterization. The
spatial resolution, contrast resolution and quantitative accuracy of the tomograms measured
with this prototype ultrasound tomograph will be determined. The ultimate goal of the
project is to develop a clinically useful ultrasound tomograph. The clinical perspeelive of
ultrasound tomography will be discussed, with the knowledge of the imaging characteristics
determined.
A short overview of the thesis concludes this chapter. In the next chapter computerized
tomography using ultrasound will be described. The measurement of the acoustic

14
parameters with the developed prototype will be discussed and the theory of the
reconstruction will be explained. The questions which algorithm is used and why the
Hartley transform is used insteadof the well-known Fourier transform will be discussed.
In chapter lil the measurement of the reflectivity will be discussed in detail, because
this is a completely new extension of the prototype. The similarities and differences with
the methods mentioned in the literature will be discussed. Some experiments on tissue-
mimicking phantoms to test the validity of the proposed concept will be shown.
The quality of the tomograms will be discussed in chapter IV. A description of the
spatial resolution, the contrast resolution and the quantitative accuracy will be given.
Phantom studies of these parameters have been performed and the results will be
presented. The effects of image quality degradation by artifacts due to refraction,
interference and phase cancellation will be discussed in the last part of chapter IV. These
image distortions prove to be an important problem in ultrasound tomography.
In chapter V the results of measurements on bone-containing structures will be
presented. The first aspect to be discussed is the question whether it will be possible to
image soft tissues accurately if there are bones in the scan plane. The second aspect
discussed is osteoporosis. Although ultrasound has been used in the diagnosis of
osteoporosis, no studies are known on ultrasound tomography in relation to osteoporosis.
Preliminary results of tomographic measurements on a rabbit femur in vitro will be
discussed. lt was also attempted to measure some parts of the hu man body in vivo. Results
of these measurements will be presented.
Finally, in chapter VI a discussion ofthe clinical perspective of ultrasound tomography
will be given tagether with the final condusion of the project and a number of
recommendations conceming ultrasound tomography.

15
11 Measurement techniques and measurement device

In this chapter computerized tomography will be described, concentrating on ultrasound

computerized tomography. The latter technique is subdivided into transmission ultrasound
tomography and reflection ultrasound tomography. In transmission ultrasound tomography
the sound pulse propagates from a transmitting transducer to an opposite receiving
transducer. Reflection ultrasound tomography uses only one transducer for transmitting a
pulse and receiving the backscattered signal.
After the description of the principles of computerized tomography, a description of the
set-up used will be given. In this set-up, transmission ultrasound tomography and reflection
ultrasound tomography are combined. A photograph of this tomograph is shown in
figure 11.1.
Subsequently, the measurements implemented in the experimental ultrasound tomograph
will be described. The measurement principles, the reconstruction conditions, the
implementation and the theoretica) precision of the implemented measurements will be
considered. The set-up providesus with four acoustic parameters: the speed of sound, the
attenuation coefficient, the attenuation slope and the reflectivity. The measurement of the
latter parameter will only be discussed in general terms. Because this is an entirely new
extension of the prototype, the physical meaning of this measurement will be discussed
separately in detail in chapter lil.
In section Il.4, the image reconstruction will be explained. Two reconstruction
algorithms used in this study will be described: the filtered backprojection algorithm and
the direct Fourier inversion algorithm. The filtered backprojection algorithm perfarms the
reconstruction in the spatial domain. The direct Fourier inversion algorithm perfarms the
reconstruction via the frequency or Fourier domain. The fundamental principle of both
algorithms is the same: the 'Centra! Section Theorem' or 'Projection-slice Theorem'. This
theorem will be explained. Since the projections are real signals, the Hartley transform
instead of the Fourier transfarm can be used. The consequences for the computing time
and memory space will also be discussed.

11.1 Principles of computerized tomography

The goal of computerized tomography is to make a cross-sectional image depicting intemal

detail of an object, such as a part of the hu man body. To be able to reconstruct such a
cross-sectional image, a set of one-dimensional data (projections) is necessary. These
projectionscan be obtained by means of X-rays (XCT), nuclear magnetic resonance (MRI),
pboton emission (SPECT), positron emission (PET), electrical impedance (EIT) or
ultrasound.

16
Figure D.l: The experimental ultrasound tomograph. Overview of the set-up (top) and top view of
the platform (bottom), showing the stepper motors and the rails which guide the transducer carriers.

17
In the case of ultrasound computerized tomography two transducers are mounted opposite
to each other and submerged in a water tank. The object to be imaged is placed between
the two transducers. The transmitting transducer sends an ultrasound pulse, which travels
through the object to the receiving transducer. Part of the energy of this pulse is scattered
back to the transmitting transducer. Infonnation about the acoustic properties of the object,
along the sound beam, is extracted from the transmitted pulse and from the backscattered
signal.
Along a linear scan, perpendicular to the sound beam, the acoustic properties are
detennined with a constant sampling interval. The data obtained along such a scan make
up a so-called projection. These projections are measured at a variabie number of angles,
equally divided over 180 '. This is elucidated in figure 11.2. Several features of the pulses
received are measured simultaneously and each feature fonns its own set of projections.
For the tomograph used in this study this will be explained in section 11.3. Tomograms of
the acoustic parameters are reconstructed from these sets of projections. This reconstruction
is done using one of the available reconstruction algorithms.
SCANNING MOVEMENTS

Figure 11.2: Schematic diagram of the measurement principle

of ultrasound computerized tomography.
The idea behind the reconstruction algorithms is that every projection of a rotational scan
has the infonnation in one direction about an acoustic property of the same slice. The
reconstruction algorithms provide us with the local value of this acoustic property. A set
of projections must satisfy some conditions to be reconstructible. These conditions follow
from the denvation of the reconstruction algorithms, which is described in section 11.4. The
conditions will be given here in advance. In section 11.3 it will be shown that these
conditions are satisfied in the measurement methods implemented. The first condition is
that the measured data must have an one-to-one relationship with a line integral of the two-
dimensional distribution of the acoustic property in the scan plane. The second condition
is that the measured object must be fully covered by a projection and the projection has
to be zero outside the object. The third condition is that the distribution of the acoustic

18
property has to be isotropie and the fourth condition says that the set of projections must
be consistent. This means that all projections have to be a projection of the same two-
dimensional distribution of an acoustic property.

11.2 Measurement device

The measurement device consists of a personal computer (PC-AT, 80286) which is

interfaced using an IEEE-488 bus both to the tomograph interface, based on a single chip
microcontroller (lntel 8751), and to a stepper motor interface. The microcontroller is
responsible for the measurement and for the control of the measuring electronics. All the
measuring electronics was designed and built in our own group. It consists of a pulse
generator, a receiver and the electronics to determine and process the features of the
ultrasound pulse received, as will be described in the next section. The microcontroller
reads the counters and AID converters and sends the data to the personal computer. The
microcontroller has a 4 kByte EPROM programming memory, into which the program is
loaded that carries out the measurements.

CAN PLATFORM
WITH STEPPER
MOTORS AND
END SWITCHES

Figure 11.3: Schematic diagram of the measurement device.

The transducers are mounted on a platform. The central part of the platform can be rotated
(figure 111). On this central part the two sets of parallel, straight rails which guide the
transducer carriers are mounted. The lateral and rotational scanning movements are driven
by stepper motors. During a measurement these stepper motors are controlled by the
microcontroller. End switches are mounted to give position information. During the
measurement of one sample, the transducers keep moving to avoid mechanica! vibrations.
Small deviations in the parallel, straight rails cause variations in the distance between
the transducers and in the direction of the sound beam duringa linear scan. Because of this
inaccuracy a 'track-error' occurs in the projections. To correct this ' track-error', one

19
projection is measured at the end of each complete rotational scan, without an object
between the transducers. This projection is subtracted from the projections, that have been
measured with an object between the transducers. The requirement that the projections are
zero outside the object is also satisfied by this 'track-error' correction.
The personal computer acts as the user-interface and data storage. In fact the personal
computer is the system controller of the IEEE-488 bus, so the user can always interrupt
a measurement and take over the control function of the microcontroller. The personal
computer is also used for image reconstruction after a complete measurement.
The platform with the transducers is placed over a water tank during the measurement.
The inner wall of this tank is covered with artificial grass to reduce unwanted reflections.

11.3 Measurement of the acoustic parameters

In this section the measurement of the four acoustic parameters, as implemented in the
ex perimental tomograph will bedescri bed. Information about three parameters is extracted
from the pulse propagating through the object. A fourth parameter is derived from the
backscattered signa! received. Transmission ultrasound tomography and reflection
ultrasound tomography are combined in one set-up.

11.3.1 Speed of sound

Speed of sound is one parameter that can be useful for tissue characterization. For this
reason velocity data of biologica! tissues were estimated by several authors. Reviews of
these data are compiled by Wells (1975), Chivers and Parry (1978) and Goss and co-
workers (1978, 1980). Greenleaf et al. (1975) firstly demonstrated the computerized
tomography concept with time-of-flight (TOF) measurements. Speed of sound can easily
be determined from the time of flight of a sound pulse. The time of flight is the time
between transmitting a sound pulse and receiving the sound pulse on the opposite
transducer.
The time of flight is determined by the speed of sound in water and the speed of sound
in the object between the two transducers. In fact it is the line integral of the inverse of
the loc al speed of sound c(v, w) on the path Lve of the sound pul se between the
transducers. The definitions of the co-ordinates are elucidated in figure Il.9.

TOF(v) - J_
L
1_
c(v,w)
dw. (ll.l)
ve
By subtracting the projection measured with only water between the transdoeers from the
projections measured with object, the condition that the projection has to be zero outside
the object is fulfilled.
In the set-up used, the TOF measurement is done using a reverberation technique
(Stapper and Sollie, 1985). Each time the receiving transducer receives an ultrasound pulse,
a putse generator is triggered and another ultrasound pulse is generaled by the transmitting

20
transducer. As mentioned before, the transducers keep moving during one sample. The
duration of an adjustable number (TPC) of reverberation cycles can easily be measured.
The reverberation method is simpler to implement than the methods described in the
literature, which use the digitized RF-signa! and extensive signa] processing (Greenleaf et
al, 1975; Carson et al., 1977; McK.innon et al., 1984) or very fast, dedicated electronics
(Giover and Sharp, I 977). Using the reverberation technique the precision can be improved
by increasing the number of reverberation cycles. Then the precision is of the same
magnitude as that of the other methods.
The detection of the sound pulse is performed by a level detector and a zero-crossing
detector. The amplifier connected with the receiving transducer has a very simple
automatic gain control and the output signa) will not be constant over the full range of the
gain controL To prevent the level detector missing one period of the sound pulse received,
the threshold level is set relative to the amplitude of the sound pulse received. The time
of arrival is defined as the time of the first zero-crossing after exceeding the threshold.
This moment has been chosen because its position in time remains unaffected by changes
of amplitude. It is only relatively little affected by the frequency-dependent attenuation in
biologica) tissue.
The duration of TPC reverberation cycles is counted by a software adjustable counting
frequency. This frequency is derived from a 100 MHzoscillator by first dividing it by 16.
This 6.25 MHz signa) is divided again by a programmabie divider which decrease the
counting frequency by a factor called TOF Time Scaler (TTS). A 16 bits counter is
counting during the TPC pulses. TPC itself is counted with another divider. After TPC
reverberation cycles the 16 bit counter is read by the microcontroller and the value is sent
to the personal computer. This is illustrated in a simplified schematic diagram in tigure
Il.4.
6 25
-- ~Hz
6.25 MHz 1 ns
--
TTS COUNTER ___.. LATCH
~

CLK

MICRO-
4 CONTROLLER

DETECTED 1
--
PULSES TPC

Figure 11.4: Simplified schematic diagram of the TOF measurement.

21
To avoid stopping of the reverberation in case a pulse is not detected, the system has a
start-up oscillator. This oscillator triggers the pulse generator to send a pulse when after
detection of a pulse the next pulse is not detected within a certain time, which is Jonger
than the longest expected cycle time.
A spurious pulse with an amplitude exceeding the threshold also can trigger the pulse
generator. This will cause reverberation at a higher frequency than the original
reverberation frequency. To suppress the possibility of receiving spurious pulses, a time
window is adqed to the circuit. During this window the receiver is disabled. If the duration
of the blocicing window is langer than half the expected cycle time, any spurious pul se wil!
die out. If the window is set to three-quarters of the reverberation cycle time, the error
caused by one spurious pulse is at worst (0.25 I TPC) * I 00% and the probability that a
pulse actually will introduce an error is maximally 25%.
The counting frequency is (6.25 I TTS) MHz. The precision of the time-of-flight values
will increase by increasing the number of reverberation cycles (TPC). The precision in
relation to the values of TTS and TPC is at worst:

precision - ---~---------- * 100%. (ll.2)

6·25 * 106 * TPC * smallest cycl e ttme
--===-- .
ITS
If TPC = 600, TTS = 12 and the smallest cycle time is 160 J.ls (common values), then the
quantization error of the counter is 0.002%, which means 3.2 ns.

11.3.2 Attenuation coefficient

The measurement of the attenuation coefficient by a comparison of the received and

transmitted energy of the sound pulse is the first application of transmission ultrasound
tomography described (Greenleaf et al., 1974). An error is introduced, because only that
part of the ultrasonic beam which is captured by the receiver is measured. The signa! loss
is therefore not only due to absorption but also due to refraction, reflection and diffraction.
In addition, it is stated that this kind of attenuation measurement is fundamentally
inaccurate for frequency-dependent media, such as tissues (Kak and Dines, 1978; Dines
and Kak, 1979). In spite of it, Sollie expected additional information from measuring peak
values and it was decided to include an amplitude measurement in the experimental
ultrasound tomograph (Sollie, 1988). From the preliminary results it appears that the
attenuation coefficient tomograms give at least qualitative, geometrical information. For
this reason the measurement is maintained in the experimental tomograph.
The reconstructibility of the amplitude measurement is based on the following equation,
which can easily be derived from the attenuation equation for the signa! amplitudes (analog
to 1.9):

Ar -
-Jn_ f !l(w) dw. (11.3)
Ar L._e

22
By measuring the received amplitude (Ar) and the transmitted amplitude (A 1) the total
attenuation along a line can be determined. Because the attenuation in water is negligible
in the frequency range normally used for medica! diagnosis (Dines and Kak, 1979), it is
assumed that the amplitude of the transmitted pulse is the same as the amplitude of the
received pulse that propagated through water only. In the software the measured values of
the received amplitudes are divided by the values of the amplitudes measured in water only
and the natura! logarithm is taken. In this way a set of reconstructible projections is
obtained. lt is clear that after applying this pre-processing the values of the projection
outside the object equal zero.
In the experimental tomograph the amplitude of the received sound pulst: is measured
using a simple electronic peak detection circuit (Sollie, 1988). The peak detector is based
on the fact that the amplitude changes only a little between two successive sound pulses.
The amplitude is compared with an output voltage on a capacitor (figure ll.S). In case of
an amplitude greater than the output voltage, the capacitor voltage is increased by a fixed
voltage (AV) by a current souree (A). A second current souree (B) decreases the voltage
continuously with a fixed voltage that is half of the possible voltage increase. In this way
the change of the output voltage is +AV/2 or -AV12 each time a pul se arrives.

INPUT PULSE
GENERATOR
OUTPUT
B

T
Figure 11.5: Diagram of the peak detecting circuit (after Sollie, 1988).

With each step of the motor that moves the transducer along the linear scan, analog to
digital conversion of the capacitor voltage is performed. An AID converter with a
resolution of 12 bits is used. This value is stared in a 16 bits software register of the
microcontro\ler. At most I 6 amplitude values are added, depending on the number of
motor steps within one sample. At the end of a sample (after TPC reverberation cycles),
the summed value of the amplitude is sent to the personal computer.
The precision of the amplitude measurement is determined by the slope of voltage
decrease over the capacitor of the peak detector, the quantization error of the Aio
converter and the number of summed values (N). If AV/2 is equal to the maximum
expected amplitude change between two pulses, the output voltage is always within AV
from the amplitude of the last received signa!. Consequently, the precision of the

23
measurement is 11V.
The amplitude of the received pulse after amplification is in the range from zero to
about 10 V. Therefore the quantization error in one conversion is less than 2.5 mV. By
adding and dividing N values (N :5; 16) this precision is increased with the square root of
N. In the worst case the precision equals 11V + 0.0025/..J(N) Volt.

11.3.3 Attenuation slope

The measurement of the derivative with respect to frequency of the attenuation coefficient,
the attenuation slope, is based on the work of Dines and Kak (1979). They proved that it
is possible to determine the integrated attenuation from the downshift of the centre
frequency of the spectrum of the received pulse.
With the assumption that the attenuation is linearly dependent on frequency and that
the curve intersects the origin (n= l and 11o=O in equation 1.10) it is possible to determine
the attenuation coefficîent from the downshift of the centre frequency. In the denvation it
is also assumed that the envelope of the pulse is a Gaussian function, that the attenuation
of water is negligible and that the centre frequency is several times larger than the width
of the spectrum. The assumption of the Gaussian envelope is satisfied as discussed in
section 1.2.
Sollie (1988) proved that the assumption that the attenuation is proportional to the
frequency is superfluous in order to determine the attenuation slope. It is only necessary
to assume that the attenuation is linearly dependent on frequency for frequencies close to
the centre frequency . The centre frequency downshift is proportional to the line integral
of the attenuation slope:

(11.4)

ro1 and ro, are the centre frequencies of the transmitted pulse and the received pulse after
transmission through a medium respectively and <Ja is a measure of the width of the
amplitude spectrum. The attenuation slope can be reconstructed by measuring the
frequency downshift, if <Ja is known. The frequency downshift is determined by
subtracting the centre frequency of the received putse transmitted through a medium from
the centre frequency of the received pulse transmitted through water only. With the
assumption that the attenuation in water is negligible the latter has the same centre
frequency as the transmitted pulse. It is clear that in this way the values outside the object
equal zero.
The centre frequency of the sound pulse can be derived from the duration of one period
of the pul se. The implementation in the ultrasound tomograph will now be describ~d. After
the received sound pulse exceeds a threshold, a zero-crossing detector is activated. This
circuit generates a pulse (U ) with the duration of half a period or a whole period. This
is elucidated in figure 116. Norrnally the duration of half a period is used in our set-up.

24
 THRESHOLD-----

I
I
I
I
I
: I I
OUTPUT
LEVEL
DETECTOR
OUTPUT
(
ZERO-CROSSING
DETECTOR

Figure 11.6: Signals concerning the period detector (after

Sollie, 1988).

It will he obvious that the same level detector and zero-crossing detector can he used in
the time-of-flight measurernent. UP wil! trigger the time window and the pulse generator.
During the duration of the UP pulse, a 100 MHz counting signal is divided by 2 in a
binary counter (figure 11.7). The 50 MHz burst is counted with a 16 bit counter. To
increase the precision, the counter is counting not during one pulse, but during all
reverberation cycles, i.e. during TPC pulses. After these TPC pulses the 16 bit counter is
read by a latch and the value is sent to the personal computer by the microcontroller.
Every time, after all pulses (TPC) are received, the counters are reset.

100 MHz 1 50 MHz

T
EHABL.E
COUNTER ____. LATCH ~

CLK

..... MICRO-
CONTROLLER

Up 1
TPC

Figure 11.7: Simplified schematic diagram of the centre frequency downshift measurement.

25
In principle the centre frequency downshift measurement is an accurate measurement,
because the frequency of the sound pulses is measured and not the peak amplitudes. The
signa! loss is not due only to absorption but also to refraction, reflection and diffraction.
To delermine the frequency of the sound pulse only a part of the pulse needs to be
captured by the receiver. How smal! this part may be allowed to become, without changes
in speetral composition, appears to be still unknown.
The precision of the centre frequency measurement is determined by the counting
frequency. A 100 MHz clock frequency is used to measure the length of half a period. The
precision is increased by counting during TPC pulses. These TPC measurements are
statistically independent. At a certain confidence level the interval, in which the period
time is detennined, can be derived.
If half the period time is 135 ns and TPC = 600 (common values), for a confidence
level of 95% the confidence interval is [134.6 ns, 135.4 ns]. This means that there is a
probability of 95% that the measured value approximates the real period time with an
precision better than 0.6%.

ll.3.4 Reflectivity

The objective of this subsection is to describe the measurement of the backscattered signa!
and the processing applied. The theoretica! foundations of this measurement wil! be
discussed in detail in the next chapter.
The three measurements described in the previous subsections use the information
contained in the transmitted pulse. The most common approach to determine the acoustic
properties of tissue, however, is to analyse the radio-frequency (RF) echo signals
containing information about the acoustic properties. The energy contained in this
backscattered signa! represents a potentially useful index for tissue characterization.
If a backscattered signa! is integrated over time, the outcome wil! be proportional to
the total backscattered energy for the corresponding sound field. The projection is formed
by these integrals along a linear scan. In this way very fast ND conversion to digitize the
RF-signa! can be avoided.
The backscatter processing circuit was designed taking into account the conditions for
reconstruction, mentioned in section H.l. A next requirement was that measurement and
the processing of the backscattered signa! should be performed simultaneously with the
other measurements.
The realization is shown in tigure ll.8. The front-end amplifier provides an initia!
amplification of the received signa!. A proteetion circuit is added at the input of the
amplifier to proteet it from being damaged by the high voltage pulse that triggers the
transducer to send a pulse. The amplifier is specially designed and uses a video amplifier
to amplify weak signals, as echo signals are. In order to account for attenuation of the
ultrasonic field as it propagates through tissue, a global time gain compensation (TGC) has
been applied. By applying an amplification that increases exponentially with time, it is
possible to compensate approximately for the attenuation.

26
 Figure 11.8: Block diagram of the backscatter
processing circuit.

A full-wave rectifier and a low-pass filter together forrn an envelope detector. The full-
wave rectifier is one also used in commercially available echo scanners.
After the envelope detector a correction circuit allows correction for both the
DC-component of the noise that is always present in addition to the backscattered signa!
and for the DC-voltage that is introduced by the rectifier. The correction should be made
before the object is placed between the transducers. The correction is done by adding an
adjustable corrective voltage to the signal. Another condition for the reconstruction
algorithm requiring zero values outside the object is also satisfied by this correction. The
integrator produces the integral over time of the envelope of the rectified signa!. The
output of the integrator is interfaced to the microcontroller by means of an AID converter.
To increase the precision, the measurement is not carried out for one transmitted
ultrasound pul se, but during an adjustable number (EPC) of ultrasound pulses. This number
has to be lower than or equal to the number of reverberation cycles (TPC), because after
TPC pulses, the measurement of a new sample is started. After EPC pulses the integrator
output is converted and sent to the personal computer.
Because of the reverberation technique, described in the subsection about the speed of
sound, it appears impossible to receive echoes from a distance further away than half the
distance between the transducers. The solution of this problem is introduetion of a constant
delay reducing the reverberation frequency.
One of the assumptions in the acoustic tissue model is an isotropie scattering. Without
this assumption the backscatter measurements perforrned from different sights would give
different results for the same region of interest. The specular echoes from interfaces that
are large with respect to the wavelength are dependent on the angle between the interface
and the sound beam. By this effect and because the assumption about isotropy is not
completely valid, the third condition for reconstruction is not fully satisfied. The.influence
on the reconstructed images will be shown in experiments.

27
11.4 Reconstruction principles

In section 1101 it is stated that it is possible to reconstruct a cross-sectional image from a

set of projectionso Several algorithms for two-dimensional image reconstruction from
projections have been publisbed (Herman, 1979)0 Sollie (1988) argued the choice of the
filtered backprojection algorithm by the fact that a very small computer (ITI 2020, an
Apple 11+-alike microcomputer) is used in the experimental ultrasound tomography systemo
On account of increasing computer power at a Jow price, this argument lost its valueo
The direct Fourier inversion method is an attractive algorithm as regards time requiredo For
this reason, the Fourier inversion method was implemented along with the filtered
backprojection reconstruction program already availableoBoth algorithms are based on the
'Centra! Section Theorem' This theorem wil! now be derived from the definition of a
0

projectiono The definition of the used co-ordinates is elucidated in tigure 11090 In the
derivation of the 'Centra! Section Theorem', the sifting property of the Dirac delta function
Ö(x) (Papoulis, 1987, po 97) is used:

(11.5)

A projection of a two-dimensional function f( x,y) at angle 0 is defined as:

p0 (v) - J j(x,y) dw 0
(11.6)
4e
Lve is the path of the sound pulse from the transmitter to the receiver. The projection
p 0 (v) is an one-dimensional function of v with the function val ues equal to all the line
integrals for a given value of 00 In practice p 0 (v) represents the data obtained with the
ultrasound tomograph at each position of the rotary tableo
If (x,y) is transformed into the co-ordinates (v, w) the projection is:

Pe(v) - f j(v cos0- w sin0,v sin0 + w cos0) dw 0

(11.7)
4e
Using the inverse sifting property of the impulse function gives:

Pe(v) - JJ f(x,y)Ö(x cose + y sin0-v) dxdy 0

(0.8)

The two-dimensional Fourier transform F(X,Y) of the function.f(x,y) with X and Yin polar
co-ordinates is:

F(R,ci>) _ JJ j(x,y)e-i21tR(xcos<I>+ysin<I>) dxdyo (11.9)

28
 Figure 11.9: Definition of the co-ordinates used in the
description of the reconstruction algorithms,
X = V cose - W sine, y = V sine + W cose.

Using the sifting property of the Dirac delta function mentioned, with v = x cos«!> + y sin«!>
as x0 gives:

F(R,«<>)- JJJ ftx,y)e - i 2 1tRvo(xcos«<> +ysin«<> -v) dxdydv. (11.10)

Substituting equations ll.8 and ll.9 gives the 'Centra! Section Theorem':

(11.11)

The right side of equation (11.11) is the one-dimensional Fourier transform of p!f>(v ):
.9j [p!l>(v)]. The theorem states that a cross-section of the two-dimensional Fourier
transform of the object at a certain angle and going through the origin equals the Fourier
transform of a projection at the same angle (figure ll.IO). Because of this physical
interpretation, this theorem is also called the 'Projection-slice Theorem'.

29
 If the two-dimensional inverse Fourier transfarm of both sides of equation 11.11 is
taken, then a basis for both the direct Fourier inversion and the filtered backprojection
reconstruction algorithm is obtained:

JJ~
Jtoo

j{x,y) _ (_1_) 2 [p<I>(v)]ei21t R(x cos <I>+ y sin<l>) 1 R 1 dRd<I> . (11.12)

21t 0-oo

Figure 11.10: Graphical representation of the central

section theorem (after Sollie, 1988).

11.4.1 Filtered backprojection algorithm

The filtered backprojection reconstruction algorithm (Ramachandran and

Lakshminarayanan, 1971) is one of the most widely used algorithms to reconstruct a
functionf(x,y) from its projections. It can be derived by again applying the sifting property
on equation (11.12):
1t

JJ[J~[p<I>(v)]ei 2 1tRviRidR]
00 00

f{x,y) - ( 2~ )2 • (11.13)
0-oo - oo
O(x cos <I> - y sin <I>- v)dvd<I>.
The product of two Fourier transfarms equals the Fourier transform of the convolution.
This leads to the condusion that if the inverse Fourier transfarm of IR I is g(v ), equation
(IJ .13) can be rewri tten as:

30
 1too

f(x,y) - (_1_) 2
21t
JJ
0-oo
[p<t>(v)*g(v)]o(xcos<l> + ysin<l>- v) dvd<l>. (0.14)

The convolution of P<t>(v) and g(v) is denoted P<t>(v)*g(v).

Formula (11.14) describes the filtered backprojection algorithm. In the denvation the
Fourier transfarm is used, whereas the fittered backprojection in itself is a spatial domain
processing technique. First, each projection is convolved with a filter function g(v ). The
next step is the backprojection of all convolved projections. This operation has a simple
geometrical interpretation. All values of a projection are 'smeared out' along the rays from
which they have been measured. This is done for all projections, each one in the direction
from which it was measured. Backprojection with the measured projections and without
convolution would result in a blurred image. The projections are 'smeared out' in the
whole plane and not only in the areas that contribute to the projection values.
For a computer implementation it is necessary to use a discrete form of the filtered
backprojection algorithm. To avoid aliasing in the spectrum the convolution filter g(v)
should be extended with a !ow-pass filter L(R):

g(v) - ~-I [IR IL(R)], (ll.15)

G(R) - IR IL(R). (0.16)

The ideal filter is limited in the frequency domain and therefore unlimited in the spatial
domain. The optima! implementation of this filter, reduced in length to realize acceptable
computing times, is rather difficult to find. A methad proposed by Cho (1974) is used to
design the filters (Sollie, 1988).

11.4.2 Direct Foorier inversion algorithm

The direct Fourier inversion reconstruction methad is also based on the validity of the
'Central Section Theorem'. This theorem states, as explained earlier, that the Fourier
transfarm of a projection at angle <l> is identical with the section through the two-
dimensional Fourier transfarm of the object taken along the line going through the origin
and with the same angle <l>. If we take the two-dimensional inverse Fourier transfarm of
both si des of the equation descrihing this theorem (II.ll) then the direct Fourier inversion
methad is represented directly (equation II.12):
1too

f(x,y) _ (_1_) 2
21t
JJ~ [p<t>(v)]ei27t R(xcos<l> + ysin<l>) 1R 1 dRd<l> . (ll.12)
0-oo

The one-dimensional Fourier transfarms of the projections P<t>(v) give F(R,<l>), which
denotes the two-dimensional Fourier transfarm of f( x,y) in a pol ar co-ordinate system.
Transformation from polar to Cartesian co-ordinates and two-dimensional inverse Fourier
transformation will givef(x,y).

31
 The most serious difficulty in this method is that F(R,<f>) is not known everywhere but
only on a fini te number of discrete points. The problem then becomes one of interpolating
from the known values in the polar co-ordinate system to values required over a
rectangular Cartesian grid (Stark et al., 1981 ). The quality of the reconstruction is
detennined mainly by the choice of the interpolation method.
In the program to reconstruct projections measured with the experimental ultrasound
tomograph three interpolation methods were implemented: nearest neighbour interpolation
(Lewitt, 1983), bilinear interpolation (Lewitt, 1983) and interpolation according to the
circular sampling theorem (Stark et al., 1981). The user is free to make his choice. The
bilinear interpolation usually gives the best result and uses the shortest processing time
(Pan and Kak, 1983).

II.4.3 Hartley transfonn in image reconstruction

In 1942, Ralph V.L. Hartley (1942) proposed a real, as opposed to complex, integral
transformation that has a more symmetrical form than the Fourier transform. Because of
the advantages it has for the realization of a reconstruction algorithm based on the direct
Fourier inversion method, we will discuss here the Hartley transform (HT). lts use in
medica! imaging has already been proposed (Paik and Fox, 1988).
The Hartley transform and its inverse (Bracewell, 1986) are defined by:

H(X) - J fix) cas(21tXx) dx, (II.17)

fix) - J H(X) cas(21tXx) dX, (11.18)

where cas(a.) = cos(a.) + sin(a.). The Hartley transform and its inverse are symmetrical
operations. This symmetry of the transform pair is a valuable feature of the Hartley
transform. A separate inversion program is not required . For image reconstruction from
projections using the direct Fourier inversion algorithm, in which both the forward
transfonn and the inverse transform are used, this is an important aspect. The key feature
of the Hartley transfonn is that it is real valued for a real valued input, while the Fourier
transfonn (FT) is complex.
The relationship between the Hartley transform and the Fourier transform F(X) is:

H(X) - Re [F(X)] - lm [F(X)] . (0.19)

As the Hartley transfonn and the Fourier transfonn are closely related the Fourier spectrum
can be calculated via the HT.
For image reconstruction from projections it is necessary to define a two-dimensional
discrete transformation. The two-dimensional discrete Hartley transform (2-D DHT) of an
objectf(x,y) and its inverse (Bracewell, 1983; Braceweil et al., 1986)

32
are defined by:

1 1 N-1 M-l Xx Yy
H(X,Y) - _ _ I: I: j{x,y) cas[21t(_+_)], (11.20)
N M x-0 y-0 N M

N-lM-1 Xx y
j{x,y) - I: I:
H(X,Y) cas[21t(_+_2)]. (11.21)
~o~o N M
A fast Hartley transfarm (FHT) can be developed in just the same way as the fast Fourier
transfarm (FFT) (Bracewell, 1984). The FHT is simply an algorithm that can compute the
DHT much more rapidly than other available algorithms. It is based on the fact that it is
possible to split the summations in the DHT into two shorter summations, which take
fewer computations.
The calculation of the 2-D DHT is usually performed by calling a succession of one-
dimensional transformations. This reduces the number of multiplications from N2 to 2N
foliowed by some additions. First, all the rows of the two-dimensional data array f(x,y) are
transformed one by one using the term cas(21tXX/N) foliowed by column-by-column
transformation using cas(21tyYIM). The outcome is not the 2-D DHT, due tothefact that
cas(a+ft) :t:. cas(a)cas(/3), whereas in the case of 2-D discrete Fourier transfarm
ia.+.fJJ = ea.efi. An additional step is needed to obtain the 2-D DHT (Bracewell et al.,
1986).
Since BraceweB developed the FHT, a number of efficient algorithms have appeared
in the literature. Dealing with real computations rather than with complex ones increases
speed and requires less memory space. Real-valued FFT algorithms are also described in
the literature (Sorensen et al ., 1987). In case two sets of projections have to be
reconstructed, it is possible to treat them as a complex signa!. That is one projection in the
real part and a projection of the other set in the imaginary part of the signal. An overall
comparison showed that FHT is faster than real-valued FFT (Bracewell, 1990). Speed of
computation of the 2-D spectrum is an important factor in image reconstruction from
projections.
To he sure that the HT can be used instead of the FT in the direct Fourier inversion
reconstruction method, the validity of the 'Central Section Theorem' for the HT has to be
proved. This proof is identical with the proof for the FT:

J P<I>(v) cas(21tRv) dv

-Jr JJ
00 00 00

j{x,y)O[xcos(cl>) + ysin(cl>) - v] dxdy] cas(2nRv) dv (11.22)

-JJ j{x,y) cas(21tRv) dxdy

-H(R,cl>).

33
When the 2-D inverse. Hartley transform is applied to the 'Centra) Section Theorem'
instead of the 2-D Fourier transform, it is better to rename the reconstruction method to
'direct Hartley inversion method'. In view of the above-mentioned advantages this method
is implemented to be used for reconstruction of the projections measured with the
experimental ultrasound tomograph.

34
111 Assessment of the backscatter measurement

This chapter comprises a detailed discussion on the measurement and processing of the
backscattered signa!. A short time after the introduetion of transmission ultrasound
tomography, the concept of reflection ultrasound tomography was described (Wade et al.,
1978; Johnson et al., 1978). In the historica! survey in the introduetion of this thesis,
subsection 1.1.2, an outline of the developments of reflection ultrasound tomography was
given. Several approaches were proposed to image the ultrasonic reflectivity distribution
of an object. In the doctoral dissertation of Sollie (1988) a few preliminary remarks were
made about measuring the backscattered signal. It was proposed to integrate the
backscattered signals over time. This can be done electronically to avoid very fast AID
conversion for the digitization of the RF-signa!. Digitizing RF-signals is also avoided in
the other measurement techniques, as described in chapter 11.
In this chapter, first the theoretica! foundation of the method, intuitively proposed by
Sollie without justification, will be described. After this the implementation wiJl be
discussed in conneetion with the theoretica! foundation . In section III.3 the results of some
experiments wiJl be described. The chapter wil! be concluded with a discussion of the
metbod developed for reflection ultrasound tomography.

111.1 Theoretica} foundation

Fan beam reflection ultrasound tomography is comprehensively discussed by Norton and

Linzer (1979a). A diagram of the measurement principle of a such a system is shown in
figure III.l. It is essen ti al that the wavefronts cover the entire width of the object' s cross-
section. The fan beam is assumed to be flat in the direction normal to the cross-section.
The theory is based on the assumption of a perfectly and weakly scattering medium,
i.e. the medium contains isolated point scatterers without mutual interactions. This is the
Bom approximation mentioned in section 1.2. Other assumptions are a constant speed of
sound and an uniform known absorption, which can be corrected for.
A short ultrasound pulse is emitted by the transducer. Scatterers that !ie at the same
distance from the transducer, i.e. on a circle with radius r and centred at the transducer
position, are reached by the acoustic wave at the same time. The backscattered waves
again arrive simultaneously at the transducer, which also acts as the receiver, and will be
summed. The resulting momentaneous output voltage of the transducer is proportional to
the total backscattered acoustic intensity for the corresponding circular are. Echoes from
larger distances arrive at the receiver later.
The recorded echoes as a function of time, an A-mode line, represent one projection,
formed by the line integrals of the ultrasonic reflectivity from all scatterers taken along the
circular are wavefronts of the diverging source. These A-mode lines are measured at a
variabie number of angles to collect a set of projections. These projections are equally
divided over 360 ' to achieve a uniform object sampling. From these projections an image

35
of the ultrasonic reflectivity is computed using a reconstruction algorithm.

''
''
y
' \
\
\
\
\
\
r \
\
\
\
x \
\
\

ae(t)
TRANSMITTER,
RECEIVER

Figure 111.1: Diagram of the fan beam reileetion tomography measurement principle and a
recorded signal.

Mathematically the projections can be described by

2r -
a 0 (t-_) J Q(x,y) dh, (ill.l)
C Hfi.r)

where ae(t) is the backscattered signa! received at the transducer position for angle e,
H 0 (r) is the circular are at distance r, dh is the incremental are length, and Q(x,y) is the
ultrasonic reflectivity distribution to be imaged.
Backprojection over the circular arcs can be expressed as:

-
Q(x,y) - J
27t
2r de,
acJ.-) (01.2)
0 c
where Q(x,y) is the reconstructed ultrasonic reflectivity distribution. This simple back-
projection wil! result in a blurred image, as explained in subsection 11.4.1. To achieve a
satisfactory reconstruction, each projection is convolved with a anti-blurring filter function
prior to backprojection. Because the projections are formed by integrations over curved
paths rather than over straight rays, the reconstruction process is more complicated than

36
the conventional reconstruction algorithms.
The approach proposed by HiJier and Ermert (1980) is analogous to the fan beam
reflection tomography described above. It is based upon a plane wave approximation
instead of a spherical wave. A transducer with a sufficiently small beam width is used in
its far field and all A-mode lines ret:eived along a linear scan are, after demodulation,
superimposed for each point of the time axis. The calculated projections are called
'pseudo-projection' because the integration is performed perpendicular to the sound beam
and is the result of a numerical summation instead of implicitly integrating during the
measurement. To obtain a uniform amplitude over the whole scan, the step size in practice
has to be smaller than the beam width, so the beam patterns overlap.

Figure 111.2: Diagram of pseudo-projection measurement principle.

37
A 'pseudo-projection' can bedescribed as

w2

p 6 (v) - Jbefy,w) dw, (lli.J)

wl

where b6 (v, w) represents a conventional parallel B-mode image under the view angle 0
and v is the spatial equivalent to echo arrival time t = 2v!c.
These projections can be reconstructed using a conventional reconstruction algorithrn.
In case of filtered backprojection reconstruction, the projections are convolved by a filter
function and backprojected after convolution. The projections are along straight lines
instead of circular arcs. An advantage is that only projections divided over 180 • are
necessary, because the other projections are the time-inverted projectionsof the measured
ones. The imaged parameter is the ultrasonic reflectivity distribution.
The method developed in this study is close to the above described plane wave
approximation method. A transducer with a small beam width is used in its far field and
the received A-mode line is integrated over time by analog electronics. This is performed
for all sample positions along a linear scan. A projection is formed by the time integrals
of the received A-mode lines. The key difference from the former method is that digitizing
the RF-signa! is not necessary. Further advantages are that the received signa! is processed
electronically and no large amount of data storage is necessary. The integral is proportional
to the total backscattered energy for the corresponding sound field .

Figure ll.3: Diagram of the reflection ultrasound tomography principle.

38
This projection is represented by the equation

v2

p 8 (w) - J b 8 (v,w) dv, (ffi.4)

VI

where b8 (v,w) is a conventional parallel B-mode image. The reconstruction is performed

using one of the well-known reconstruction algorithms.
In the continuous form this will give exactly the same result after reconstruction as the
method mentioned above. The use of a computer to perform the measurement and the
image reconstruction necessitate some remarks about quantization.
In the 'pseudo-projection' method the A-mode line is digitized with a sampling rate that
must satisfy the Nyquist criterium. The bandwidth in the backscattered signals approaches
10 MHz, which implies a sampling rate of 20 MHz. This sampling rate correspondents to
a spatial sampling interval of 0.075 mm in water. After digitizing the signa! is rectified,
!ow-pass filtered and resampled to the desired spatial resolution.
The sample distance for the method developed in this thesis is connected with the
length of a motor step and the number of motor steps per sample. The length of a motor
step intheset-up used is 0.106 mm. The fact that the transducer keeps moving during one
sample acts as a spatial !ow-pass filter. The number of samples can be chosen at the start
of the measurement.

The reflection ultrasound tomography method developed in this thesis will be called
integrated backscatter measurement, because the A-mode lines are integrated during the
measurement. However, the imaged parameter in the tornogram is the ultrasonic
reflectivity. The integrated backscatter (IB) itself is a widely applied parameter in
ultrasonic tissue characterization. Integrated backscatter is defined as the frequency average
of the backscatter transfer function over the band width of the insonifying transducer
(O'Donnell et al., 1979). The backscatter transfer function describes the energy efficiency
of the ultrasonic backscatter from the tissue sample at each frequency. The integrated
backscatter can be expressed as the ratio of the energy in the signa! backscattered from the
volume of tissue to the energy reflected from a standard reflector:

f +fl1f I V(f) 12 (III.S)

IB - lO log 10 dj,
f- l1f I P(f) 12
where I V(j) 1 2 is the fower spectrum of the backscattered signals arising from the volume
of tissue and I P(f) I is the reference power spectrum. M is half the usabie band width.
The IB is expressed in dB .
The Fourier transform of the backscattered signa! is:
(ID.6)

where B(j) is the backscatter transfer function and f2(f) describes the propagation effects
such as the attenuation.
The forma! procedure to calculate the integrated backscatter is to correct the

39
backscattered signa! for the attenuation (i.e., r(f)) and calculate the power spectrum. The
power spectrum of the signa\ scattered back from tissue has to be corrected for the
characteristics of the measurement system. This is done by measuring the backscattered
signa! of a planar reflector, usually a flat stainless steel plate, and calculate a reference
power spectrum. The m is then calculated by averaging over the useful frequency range.
In the literature different methods for calculating the m are reported . The correction for
the system characteristics is sometimes omitted (Rijsterborgh et al., 1990) or the processing
takes place in the time domain (Thomas et al., 1989, Picano et al., 1990). An advantage
of time domain signa! processing is that it can be performed in real-time.
Using Pareeval's theorem, equation III.5 can be described as:

IB- 10log 10 f
"t+Ó"t: 2
lv(t)l dt, (III.7)
"[ -Ó"t: lp(t) 12
where v(t) and p(t) are the backscattered signals from the volume of tissue and the
standard reflector, respectively. The backscattered signals are squared and integrated over
a time interval. The time domain processing becomes more easy to realize if the signa! is
not squared but only rectified and integrated over the time interval.
Rijsterborgh et al. (1992) compared six different methods to calculate the IB, either in
the frequency domain or in the time domain. One of the methods described is using a time
domain processing without correction for the characteristics of the measurement system.
The signa! is rectified instead of squared. Even though this method is theoretically
incorrect to measure the signa! power in the time domain, his study shows no major
difference from the forma! method (gold standard), except the significant difference in
offset level. From this study, it can be concluded that the squaring of the signa! before
integrating can be omitted and it is sufficient to rectify the signa! to obtain a measure of
the backscattered power.
The reflection ultrasound tomography method developed in this thesis measured the
integral of the rectified backscattered signa! along a linear scan:

v2

pEf._w) - JI b6 (v,w) I dv . (III.S)

VI

The projection has a close analogy to the m. After reconstruction a tornogram of the
reflectivity distribution, b6 (v, w ), is the result.

111.2 lmplementation of the integrated backscatter measurement

The method developed in section 111.1 is implemented in the ultrasound tomograph and the
backscattered signals are measured simultaneously with the transmission measurements.
A description of the implementation was given in subsection 11.3.4. In the current section
this implementation (figure 11.8) will be discussed in relation to the theory from the
previous section.

40
 After the pre-amplification a time-gain controller is applied to compensate for the
attenuation. An exponentially increasing amplification has been chosen. It would be more
accurate to compensate the attenuation during the reconstruction, using the simultaneously
measured attenuation coefficient tomogram. A disadvantage in that case is that the
backscattered signals have to be stored. A more advanced TGC, as in modem echo
devices, would he a practical improvement. With the advanced TGCs, the operator can
influence the gain-compensation profile and adapt the gain to the object under study.
Subsequent to time-gain compensation the signa! is rectified foliowed by integration
using analog electronics. Although theoretically not correct, as explained in the previous
section, the outcome is still a measure of the backscattered power. The method is a time-
domaio processing method with the advantages of reai-time performance.
Absolute calibration of the values of IB relative to a perfect reflector cannot be
obtained with the tomographic system. The measurement is controlled by the reverberation
concept used for the time-of-flight measurements. Interruption of the sound beam with a
perfect reflector will disturb the reverberation necessary for the transmission measurements.
For this reason the reconstructed reflectivity values are in arbitrary units.
In the reconstruction software the number of reverberation cycles during which the
integration was performed is compensated for. In section II.3 the presence of a De-
component and the correction circuit were descri bed. The DC-component, which is present
in spite of the hardware correction, is compensated for in the software. This is done by
subtracting the mean DC-Ievel from each projection. The hardware correction is still
necessary to make use of the full dynamic range of the integrator.

111.3 Experiments

The assumptions made in section lil. I (Bom approximation, constant speed of sound,
known attenuation) wiJl, of course, break down to some degree when we measure in real
materiaL The aim of this paragraph is to test the validity of the proposed concept and to
show some experimental results and the image degradation. All the measurements w,ere
performed on tissue-mimicking phantoms.
The manufacturing of the phantoms will he explained in detail in section IV.l. At this
place it will suffice to mention that the basic material of the phantoms is agar gel.
Iron(ill)oxide powder will be added during manufacturing to influence the scattering
properties. The shape of the phantoms is cylindrical (!ll 50 mm) and an intemal structure
was arranged by Jeaving open spaces during manufacturing or cutting out parts of the
phantom afterwards and filling the holes with phantom material of a different composition.
In all the following measurements two unfocused, 3.5 MHz transducers (Panametrics
model V384, !ll6.25 mm) were used. The number of projections for each measurement was
in the range from 80 to 100. It was found that this gives acceptable results and more
projections did not significantly improve the image. The number of samples per projection
was 64 and the lengthof the linear scan was 8.14 cm. The number of reverberation cycles
for each sample (TPC) was 600 and the IB was measured during 550 (EPC) cycles. The
meaning of these parameters has been explained in chapter 11. The used reconstruction

41
program is based on the direct Fourier inversion algorithm. The tomograms were
reconstructed on a 64 x 64 grid. In the tomograms the grey scale is taken such that the
highest value within the image is white and the lowest value is black. The graduated scale
next to the tornogram shows the corresponding numerical values.
The reflectivity tornogram of a homogeneous phantom with 1.5% iron(lll)oxide powder
added is shown in figure Ill.4. This measurement served to investigate the acoustic
properties of this phantom material and to check the homogeneity of the phantom. On the
right side of the figure a norrnalized cross-section through the tornogram at the indicated
position is shown.

0 _5 REFLECTIVITY

9 17 25 33 40 48 58 84

SAMPLE NUMBER

Figure 111.4: Reflectivity tornogram (left) of a homogeneaus phantom and a cross-section through
the tornogram (right).

The mean values of the acoustic properties were deterrnined in a circular region of interest
(ROl) matching the whole cross-section of the phantom. The mean speed of sound in the
phantom is 1486 ± 1 m/s, the attenuation coefficient is 0.80 ± 0.12 dB/cm, the attenuation
slope 0.42 ± 0.15 dB/cm MHz and the mean value of the reflectivity is 0.23 ± 0.08
arbitrary units. The speed of sound is close to that of water (1482 m/s) and therefore
deviations due to refraction, which will be discussed in chapter IV, will be avoided. The
results of these measurements showed no indication that the phantom is not homogeneous.
The cross-section illustrates that the reflectivity tornogram contains much noise. In spite
of this noise the phantom is clearly visible as a structure scattering more than the
surrounding water.
Figure ill.5 shows the results of the measurement of a phantom with three cylindrical
inserts with 1.5 % iron(III)oxide. The bulk of the phantom consists of pure agar gel. The
result shows that the strongly scattering cylindrical structures in a weakly scattering
surrounding are visible. The circular geometry of the inserts is not well defined in the
reconstruction. The edge of the phantom is visible as a bright ring. The bright spot in the
rniddle of the cross-section of the phantom is an artifact.

42
 !liS mmo

!11 10 mm

Figure lli.S: Diagram of the geometry (left) and the reflectivity tornogram (right) of a phantom
with three cylindrical inserts with 1.5 % iron(III)oxide.

As visible in the reflectivity tomograms, they show a bright spot in the middle of the
phantom. This is caused by a specular reflection when the sound beam is exactly
perpendicular to the tangent to the phantom. To illustrate this more clearly, a weakly
scattering phantom of pure agar gel was measured. In figure ill.6 a tornogram and a
projection are shown. In the projection the distortion caused by the specular reflection is
visible. Artifacts at the edges of the phantom are also clearly visible. The latter artifacts
are visible in the reconstruction as the bright circle on the edge of the phantom.
Figure ill.7 shows the attenuation coefficient tornogram and the reflectivity tornogtarn
of a phantom (1.5% iron(III)oxide) with a triangular and a circular cylindrical hole in it.
The diameter of the circular insertion is 10 mm and the triangular insertion is a quarter of
a circular cylinder with a diameter of 30 mm. The holes are filled with water, when
submerged in the water tank. This experiment served to show whether it is possible to
image a non-scattering structure (water-filled hole) in a strongly scattering surrounding.
The attenuation coefficient tornogram is shown to display the geometry of the phantom.
Both holes are visible in the reflectivity tornogram aS weakly scattering (dark) areas. The
edges of the structures are not very sharp in the reconstruction.

43
 0. 8 REFLECTIVITY

8 16 22 29 38 43 60 67 84

SAMPLE NUMBER

Figure 111.6: Reflectivity tornogram (left) and projection (right) with clear specular reileetion
artifact.

Figure 111.7: Attenuation coefficient tornogram (left) and reflectivity tornogram (right) of a phantom
with two inserts, filled with water.

Figure 111.8 shows the attenuation and reflectivity tomograms of a scattering object with
a re-entrant angle. It was suspected that a receding structure might cause problems in the
reconstruction of the reflectivity tomogram, due to eclipsing by the scattering medium. The
result shows that this is not the case. The geometry in the tornogram is in agreement with
the real phantom geometry.

44
Figure 111.8: Attenuation coefficient tornogram (left) and reflectivity tornogram (right) of a phantom
with 1.5 % iron(III)oxide.

Observation of the tomograms of the reflectivity leads to the condusion that they generally
give a clear representation of the geometry of the internal structure of the phantoms.

10.4 Discussion

This chapter demonstrales the feasibility of implementing reflection ultrasound tomography

without digitizing the RF-signals, but with inlegration of the A-mode signals by analog
electronics. Reflectivity tomograms of tissue-mimicking phantoms illustrate the
performance of the technique. Scattering structures in weakly scattering surroundings and
vice versa are visualized correctly.
The quality of the reflectivity tomograms itself is not good. The reconstruction results
in a noisy image, so that small details are not visible. The edges of structures are not
sharply defined. Specular reflections of a circular structure will be reconstructed as a
strongly scattering spot in its centre.
Another drawback of the method is that the reconstructed values are in arbitrary units.
The results are not camparabie with data from the literature in a quantitative sense. The
simultaneous measurement of a calibration phantom with known scattering properties
would have been a salution to obtain an absolute quantitative scale.
Camparing the results with those from the literature obtained with computer-aided
compound scanning (subsection 1.1.3) shows that the quality of the reflectivity tomograms
is considerably poorer (Röhrlein, 1986; Jago and Whittingham, 1992). This method,
mentioned in section 1.1.2, superimposes several B-mode images measured under different
angles, after convolution with an appropriate filter. Digitizing of the RF-signa) is
necessary.
Because of the very rapid development of commercially available hardware in the last
decade and the sharply fallen prices, digitizing the RF-signa! is no Jonger in conflict with
the projeet's initia! main goal. The requirement of cheap and unsophisticated equipment

45
is feasible with the currently available digitizing boards which can be plugged into a
standard PC. This option has not yet been investigated.
A valuable feature of the set-up is the simultaneous recording of transmission and
reflection data. If the aim is to characterize tissues rather than increasing the resolution of
the conventional echogram, it would appear from the results obtained so far that the
reflectivity tornogram could give information in addition to that of the three tomograrns
obtained from transmission measurements. The reflectivity tornogram can provide
geometrical information and an extra parameter in the multi-parameter measurement, which
already determines the speed of sound and the attenuation of ultrasound. It is clear,
however, that improvements in data acquisition and analysis must be made before this
technique could be used widely.

46
IV Assessment of the performance of the tomograph

This chapter deals with the assessment of the tomograms obtained with the experimental
ultrasound tomograph described in chapter TI. For medica! imaging and tissue
characterization, the most important characteristics are spatial resolution, contrast resolution
and quantitative accuracy.
The spatial resolution or resolving limit of an imaging system is the minimum distance
between two objects that can be distinguished as two entities. Historically the resolving
power of a telescope was described by the minimum angular separation of two stars that
could be distinguished as two objects. In the literature, many clinical tomograms are shown
with a disappointing spatial resolution. This justifies further research into resolution, under
controlled conditions.
Contrast resolution is a measure of the ability to distinguish objects with acoustic
properties that differ a little from their surroundings. Because of the small differences in
the acoustic properties of tissues that are of interest in clinical practice, contrast resolution
is an important characteristic of an ultrasound tomographic imaging system.
Quantitative accuracy is a measure of the correctness of the match between the values
of the acoustic properties of an object and the values in the reconstructed images. This is
an important characteristic of the tomograms for assessing the potential clinical use of
ultrasound tomography as a tissue characterization technique.
In ultrasound tomography these characteristics are influenced by several physical
phenomena. Many studies have been performed on the reduction of the artifacts caused by
these phenomena (Klepper et al., 1981; Schrnitt et al., 1984b; Fitting et al., 1987). At the
end of this chapter, refraction, interterenee and phase cancellation will be discussed
extensively.
In the first section of this chapter, the composition and the manufacturing of tissue-
mimieicing phantoms that have been used in the measurements will be described. Our
standard measurement protocol for phantom studies will also be presented .

IV.l Measurements on phantoms

IV.l.l Tissue-mimicidog phantoms

Tissue-mimicking phantoms are often used for assessing the performance of ultrasound
equipment. These phantoms have known acoustic properties and a known geometrical
structure. One of the requirements of the phantom material is that the acoustic properties
should resembie those of biologica! tissues. Another requirement is that these properties
are independently controllable in the manufacturing process.
The existing, commercially available phantoms, designed for ultrasound equipment
testing, quality control and training, have an acrylic case with one or two sides that have
a membrane window as scanning surface. These 'standard' phantoms are not suitable for

47
use in the ultrasound tomograph, because it is impossible to perform a transmiSSIOn
measurement over an angle of 180·. Therefore, the phantoms used in this study were
manufactured in our own laboratory.
An accepted tissue-rnirnicking material is agar gel, in which n-propanol concentration
determines the speed of sound (Madsen et al., 1978; Burlew et al., 1980). The attenuation
and scattering properties can be influenced by adding graphite powder, iron(III)oxide
powder (Fe20 3 ) or silicon carbide grinding powder (Mesdag, 1985). The manufacturing
process of these phantoms is not very difficult, the phantoms are easy manageable and they
are reproducible.
The phantoms used in the experiments described in this thesis were prepared by boiling
3% dry agar powder with distilled water for about half a minute. The mixture was
continuously stirred during warming up and boiling. The solution was poured into
cylindrical moulds (16 5 cm) and any visible bubbles were removed. For better
homogeneity, the congealing process has to be speeded up. For this purpose, the moulds
were placed in a tank with cold water. The speed of sound was influenced by adding n-
propanol afterwards by diffusion. The attenuation and scattering properties were influenced
by adding iron(III)oxide powder during manufacturing, before warming up the mixture.
The internal structure of the phantoms was created by leaving open holes during
manufacturi~g or cutting out parts of the phantom afterwards and filling the holes with
phantom material of an other composition.
To prevent desiccation, the phantoms were stored in distilled water or in case of
phantoms with n-propanol added, in a solution of n-propanol of the same concentration.
The experience of our own group is that the phantom properties remain unchanged for at
least 6 months. The only problem is bacterial invasion. To avoid degradation of the
phantom, the water should be refreshed regularly. In this way the phantoms can be used
for long periods.
The experimentalset-up was not optimized forspeedof data acquisition. Consequently,
we need phantoms that are stabie through time. Tbe n-propanol diffuses out of the
phantoms when submerged in the water tank. To be sure this will not significantly
influence the concentration of n-propanol during a measurement, we determined the
diffusion rate of n-propanol in the phantoms.
Two phantoms with 5 and 10 percent n-propanol were measured several times during
a week and between the measurements stored in a large tank of pure water. The average
speed of sound in a smal! region of interest at the centre of the phantom was determined
from the tomograms.
Figure IV.l shows the speed of sound, influenced by the percentage of n-propanol, as
a function of the time after the first measurement. The curve is the best fitting salution of
the diffusion equation. This tigure shows that the diffusion rate of n-propanol into water
is low, compared to the duration of one measurement, which is about 15 minutes.

48
 1600 SPEED OF SOUND (mts)

- THEORETICAL CURVE
1580
~ 10% N-PROPANOL 0,+ MEASURED DATA POINTS
- /
1580

1540

1520

1500

1480 O.U....""-'"~......w~w......~u.........=...J~llllL~o.u.Lu~U.U.....~.............J

0 10 20 30 40 50 80 70 80 90 100

TIME (HOURS)

Figure IV.l: Speed of sound in the centre of the phantom as

a function of time.

IV.1.2 Standard measurement protocol for phantom studies

The measurements were performed, unless other-wise stated, under so-called standard
conditions. These will be described in this section. The consequences of the adjustments
were explained in section II.3. As explained in chapter 11 the local speed of sound, the
local attenuation coefficient, the local attenuation slope and the local reflectivity are
measured simultaneously.
Two unfocused, 3.5 MHz transducers (Panametrics model V384, !iS 6.25 mm) were used
in the experiments. The transducers were about 15 cm separated. The measurements were
carried out at room temperature (20 ± 2 'C). The speed of sound in distilled water at this
temperature was taken to be 1482 m/s (Greenspan and Tschiegg, 1959). The width of the
transmitted ultrasound pulse (aT), determined from the received pulse without object
between the transducers, is 0.31 ~s. These values were used for the post-processing from
time of flight tospeedof sound and from frequency shift to attenuation slope, respectively.
Before the start of the measurement the transmitter and receiver were aligned, so that the
received amplitude has a maximum value. Then the transmitter and receiver are exactly
opposite to each other.
The number of projections for each measurement ranged from 80 to 100. This number
of projections is sufficient for a reliable reconstruction. The number of samples per
projection was 64. The total scan length was 8.14 cm, which implies that the sample
distance was 1.27 mm. The number of reverberation cycles per sample was set to the
optima! value of 600. The counting frequency of the TOF binary counter was 521 kHz
(100 MHz I (16 x 12)). These conditions were chosen to avoid an overflow of the counter
for the largest expected time of flight.
If necessary, recognizable error spikes were removed from the time-of-flight projections
before reconstruction, by linear interpolating between the previous and following sample.

49
These isolated spikes would cause streaks in the tomogram.
The reconstruction program used is based on the direct Fourier inversion algorithm,
explained in section 11.4. The transformation from the polar co-ordinate system to the
Cartesian system, prior to two-dimensional inverse Fourier transformation, requires
interpolation. This was done using a bilinear interpolation algorithm. The image size of the
tomograms is 64 x 64 pixels.
In the tomograms shown in this thesis , white has been chosen to indicate the highest
value of the acoustic parameter and black the lowest one. The dynamic range of all the
grey levels was automatically scaled to fill the full range in the tomograms . Black does not
necessarily represent the same value in each tomogram, but only the lowest one in that
particular picture. In the printed tomograms the total number of grey levels, including
black and white, is 33. On the computer monitor the tomograms are displayed in either 16
or 64 grey levels, depending on the graphics mode.
For quantitative analysis of the tomograms a region of interest (ROl) will be outlined
in the tomogram. In this ROl the mean value and standard deviation of the local acoustic
property were calculated. This ROl was defined at some distance of the border between
two structures to avoid artifacts at the border distarting the determination of the mean
values.

IV.2 Phantom study of spatial resolution

IV.2.1 Introduetion

An important characteristic of the ultrasound tomograph is the ability to show smal]

details . The ability of an imaging system to distinguish objects situated closely tagether
is called spatial resolution. There is no universally accepted way of measuring spatial
resolution . One way is to quote the modulation transfer function (MTF), measured from
a bar pattem. The MTF is a measure of the contrast transfer from object to image as a
function of the object size. Bar pattem test objects are hard to make. Therefore, a more
common and accepted way of checking the resolution limit is to find the smallest high
contrast object in a phantom that can be seen in a reconstructed picture. The most common
but non-quantitative approach to do this, is by visual evaluation of the image of a
resolution phantom.
In advance it was not clear which phantom displays the highest contrast in the
tornogram and therefore a set of phantoms with increasing contrast was used in this study.
The tornogram with the most visible elements is chosen to determine the spatial resolution
limit.
The size of the smallest object that can be seen on a tornogram depends among other
things on the image noise. When scanning the water tank without object, the tornogram
should appear as a uniform shade of grey, but in fact it shows a speekled appearance. The
noise is introduced by the measuring hardware, by the movements of the transducers and
toa lesser extent to the reconstruction process (Sollie, 1988). This noise can be quantified
by the standard deviation of the distribution of reconstructed values. This distribution is

50
of the type known as a Gaussian distribution. For example, in figure IV.2 the attenuation
coefficient tornogram of a noise measurement is shown, together with the distribution of
the reconstructed values, the best fitting Gaussian curve and the residual errors. The other
three acoustic parameters produced analogous results.

1.00 NORMALIZED NUMBER OF PIXELS

_ _ UEASURED NOISE

\ --- - - FITTED CURVE

a • 0.02 dBiom
....

-D.10 ·0.05 .0.00 .... 0.10

ATTENUATION COEFFICIENT (dB/cm)

(b)

o.•• RESIDUAL ERRORS

(a)

·0.10 · 0.05 .0.00 0.05 0.10

ATTENUATION COEFFICIENT (dB/cm)

(c)

Figure IV.2: Noise in the attenuation coefficient measurement. (a) Tomogram. (b) Distribution of
reconstructed values and best fitting Gaussian curve. (c) Residual errors of the fit.

In the tomograms, measured with the standard protocol and no object in the water tank,
the standard deviation is 0.2 mis in the speed of sound tomogram, 0.02 dB/cm in the
attenuation coefficient tomogram, 0.11 dB/cm MHz in the attenuation slope tornogram and
0.04 arbitrary units in the reflectivity tomogram.
The phantoms used in this study of the spatial resolution in the tomograms were 5 cm
in diameter and had eight circular cylindrical holes that fill with water when submerged.
The diameter of the holes ranges from 1 mm to 6 mm (figure IV.3). The contrast between
the bulk and the holes has been influenced by adding n-propanol or iron(III)oxide powder
to the bulk materiaL This causes the values of the acoustic properties of the bulk to be
always higher than those of the holes. The standard measurement conditions were
employed.

51
 hole diameter
1
6 mm
2 4 mm
8 0 2

3 2.5 mm
0 0
3
4 1.5 mm 07 0
5 mm
8 4
6 2 mm 0 0
5
7 3 mm 0

8 5 mm

Figure IV.3: Diagram of the geometry of the resolution phantoms.

IV.2.2 Results

In this section the results are shown of some measurements using phantoms with the
geometry outlined in tigure IV.3. The orientation of the phantoms in the tomograms is not
necessarily the same as in that diagram. In the tomograms of different measurements the
orientation is mutually also different. This is caused by a rotation of the phantom during
the positioning in the watertank prior to the measurement. The position of the phantom is
not exactly reproducible. The largest hole is indicated in the tomograms with an 'I' to
illustrate the position.
The tomograms were evaluated visually when displayed on the computer monitor. In
some cases more detail is visible than on the printed tomograms, as presented here. Visual
evaluation is a subjective method, but in clinical practice this will also be the tirst step in
characterizing tissues using tomograms.
Speed of sound data were collected for phantoms with increasing percentages of
n-propanol. The tornogram with the largest number of visible holes was selected and
displayed in tigure IV.4. This is a tornogram of a phantom with 4% n-propanol added . The
difference in the speed of sound between the phantom and water is 30 m/s (2.0% contrast).
This value has been measured earlier with the tomograph. Some of the water-tilled holes
are easy to perceive as dark spots in a brighter phantom. The smallest visible hole has a
diameter of 1.5 mm.
Atteriuation was measured in phantoms with iron(III)oxide added. In tigure IV.5 the
tornogram of the attenuation coefficient and in tigure IV.6 the tornogram of the attenuation
slope of a phantom with 0.4% iron(III)oxide are displayed. The attenuation coefficient of
this phantom material is 0.43 dB/cm and the attenuation slope 0.06 dB/cm MHz, as
measured earlier. In the attenuation coefficient tornogram all holes are visible. In the
attenuation slope tornogram only the smallest hole with a diameter of I mm is invisible.
In the reflectivity tomograms of both the phantoms with n-propanol and the phantoms
with iron(III)oxide powder added, none of the water-tilled holes is visible. An example of
these tomograms is displayed in tigure IV.7.

52
Figure IV.4: Speed of sound tornogram of a Figure IV.S: Attenuation coefficient tornogram
phantom with 4% n-propanol added. of a phantom with 0.4% iron(III)oxide powder
added.

Figure IV.6: Attenuation slope tornogram of a Figure IV.7: Reflectivity tornogram of a

phantom with 0.4% iron(III)oxide powder phantom with 4% iron(III)oxide powder added.
added.

IV.2.3 Discussion

The results of the measurements indicate that the resolution limit of the experimental
ultrasound tomograph is about 1.0 - 1.5 mm, in case of the speed of sound, the attenuation
coefficient and the attenuation slope measurement. This is of the same order of magnitude
as the sample distance.
The tornogram of the speed of sound shows a rather homogeneous speed of sound of
the phantom bulk itself. The borders of the holes are not sharply defined in the
reconstruction.

53
 In the tornogram of the attenuation coefficient the holes show a value of the attenuation
coefficient that can not be correct. The attenuation coefficient in water is assumed to be
0 dB and in the reconstruction the attenuation coefficient values are negative. This artificial
contrast makes it easier to perceive the holes.
The relative noise that can be derived from the noise measurements presented in section
IV.2.1, is the largestin the attenuation slope tomograms. The more noise is apparent in the
tomogram, the more difficult it is to distinguish small structures. Ring-shaped artifacts are
visible in the tornogram around the phantom and the holes. In case the holes are close
together, these artifacts will influence the perceptibility negatively.
The results show that the holes in the phantoms are too small to become visible in the
reflectivity tomogram. This poor spatial resolution is caused by the noisy character of the
tomogram.

IV.3 Phantom study of contrast resolution

IV.3.1 Introduetion

Because of the small differences in the acoustic properties of the tissues that are of interest
in clinical practice, contrast resolution or low contrast perceptibility is an important
characteristic in the assessment of ultrasound tomography as a tissue characterization
technique. The contrast resolution of an imaging system is recognized as at least of equal
importance as spatial resolution.
A complete description of contrast resolution is furnished by a contrast-detail visibility
diagram (C-D diagram). Such a diagram describes the ability of the total scanning-
irnaging-observer system to detect, display and recognize structures that !ie at the threshold
of human vision. A C-D diagram is obtained from a tornogram of a phantom that contains
structures of various sizes that differ slightly in acoustic properties from their surrounding
homogeneaus medium. The C-D diagram is obtained when the contrast in the phantoms
is plotted against the sizes of the structures in the tomograms and then it is indicated
whether a structure is visible or not.
A phantom contrast resolution study of the tomograms measured with the experimental
ultrasound tomograph, was performed. The phantoms contained structures differing only
slightly from their surroundings in the acoustic properties. The phantoms used were the
same as the phantoms described in the previous section. The contrast between the bulk and
the holes was influenced by adding n-propanol or iron(ill)oxide powder to the bulk
materiaL The measurements and reconstructions were carried out under the standard
conditions. The tomograms were examined visually by the author when displayed on the
computer monitor. Because of the poor spatial resolution of the reflectivity tomograms, no
C-D diagram was constructed for the reflectivity.

54
IV.3.2 Results

The results of the contrast resolution experiments are presented as C-D diagrams. The
contrast is expressed as the difference (~) in value of the acoustic property between the
bulk and the water-filled holes. In tigure IV.8 the C-D diagram of the speed of sound is
shown. In tigure IV.9 the C-D diagram of the attenuation coefficient and in tigure IV. IO
the C-D diagram of the attenuation slope are shown.

100 ll. c (m/s)

80 0 + + + + + + +

60
0 + + + + + + + + VISIBLE
0 0 + + + + + +
0 INVISIBLE
40
0 0 + + + + + +

20 0 0 + + + + + +

0 0 0 + + + + +
0
0 2 4 6

DIAMETER (mm)

Figure IV.S: Contrast detail visibility diagram of the speed of sound.

s.oo ll. a (dB/cm)

0 0 0 + + + + +
2.40

1.80 + VISIBLE

0 INVISIBLE
1.20
0 + + + + + + +

0 + + + + + + +
0.60 0 + + + + + + +
0 + + + + + + +
0 + + + + + + +
0 + + + + + + +
0 .00
0 2 4 8

DIAMETER (mm)

Figure IV.9: Contrast detail visibility diagram of the attenuation coefficient.

55
 1.00 b. 'öa/'ö!J> (dB/ MHz cm)

0.80 0 0 0 + + + + +

0.80 + VISIBLE

0 INVISIBLE
0.40 0 0 + + + + + +
0 + + + + + + +

0.20 0 + + + + + + +
0 + + + + + + +
0 0 + + + + + +
0.00
0 2 4 8

DIAMETER (mm)

Figure fV.lO: Contrast detail visibility diagram of the attenuation slope.

IV.3.3 Discussion

The C-D diagram of the speed of sound shows the expected results. With increasing
contrast, smaller details become visible. With a speed of sound difference of only 8 m/s
between the bulk materialand the water, holes with a diameter as smallas 2.5 mm are still
visible.
The C-D diagrams of the attenuation coefficient and the attenuation slope show the
same appearance. In the low contrast region, the visibility of structures is very weakly
dependent on contrast. With increasing contrast, the visibility decreases. At contrasts higher
than plotted in the C-D diagrams, the minimum size of the visible holes increases more.
At very high contrast for both the attenuation coefficient and the attenuation slope, no
internal geometry of the phantom is visible.
The explanation is that relative to the noise the received acoustic signa] of the
amplitude measurement is too small to do an accurate measurement. The measurement of
the zero crossings to determine the attenuation slope is also inaccurate. These high
contrasts are only artificial and do not occur in biologica! tissues. In practice this would
therefore not cause any problem.

IV.4 Phantom study of quantitative accuracy

The goal of ultrasound tomography is to generate quantitative images based on acoustic

properties in which the numerical values provide estimates of the Iocal value of the

56
specific acoustic property of the object. Quantitative accuracy is an indication of the
differences between the mean value of a ROl and the real value under the conditions of
the measurement. Although this is an important image parameter in assessing the potential
clinical use of ultrasound tomography as a tissue characterization technique, no detailed
study has been published. This section deals with quantitative accuracy.
The acoustic properties of the home-made phantoms are unknown. A methad to
delermine the quantitative accuracy of the tomograms is to campare the values with the
results of a reliable, direct measurement technique. In actual fact the values of the
tomograms have been compared with the results of experiments with a system based on
the concept of the scanning acoustic microscope, referred to as the ultrasound macroscope
(Foster et al., 1984). This wil! be described in the fust part of this section.
It is expected that the quantitative accuracy of the tomograms will bedependenton the
size of the structure to be imaged. A phantom study of the relationship between the size
and the quantitative accuracy is the topic of the following part of this section.

IV.4.1 Quantitative characterization using an acoustic macroscope

The goal of the experiment described here is to campare the quantitative results obtained
with the ultrasound tomograph with a direct measurement technique. The instrumental set-
up and data acquisition used are described elsewhere (Van der Steen et al., 1991).
Therefore, only a short description wil! be given here.

Methad (according to Van der Steen et al., 1991)

A diagram of the set-up is shown in tigure IV. I!. A flat slice of the phantom with a
unknown exact thickness was placed in the water tank on a glass block that served as an
ultrasonic mirror. A membrane was put on top of the slice to enhance the flatlening of the
phantom sample. The transducer was the same as used in the tomographic system. The
transducer was moved in the XY-plane in a raster pattern of 7 x 7 samples, at a distance
of I mm apart.
The measured signals are shown schematically in tigure IV .12. The RF-echo signa! was
measured under three conditions:
(I) The reference signa! was measured without phantom sample and was -20 dB
attenuated at the input of the pulser/receiver.
(2) The reflection from the front of the phantom sample and the reflection from the
glass mirror were measured with the same attenuation as the reference signal.
(3) The backscattered signa! was measured with 0 dB attenuation.
The attenuated and !ow-pass filtered signa! (fourth order Bessel filter, cutoff frequency
15 MHz (-3 dB)) was digitized at 25 MHz and stared in the computer. From the measured
signals, the speed of sound, attenuation and the backscatter were calculated.

57
 D I E3 I
PC-AT ~

IEEE-4118

PULSER/RECEIVER LOW-PASS riLTER

SlOHAL AHALYSER

PULSt GENERATOR

Figure IV.ll: Schematic diagram of the setup of the acoustic macroscope.

The speed of sound in the phantom sample with unknown thickness was estimated from
the measurements of the difference in time of flight of the glass mirror reflection without
(t0 ) and with phantom sample(~) interposed and the time of flight of the reflection of the
front of the phantom sample (t1). The centroid estimation of the peak of the envelope of
the reflected pulse (Kontonassios and Ophir, 1987) was used todetermine the arrival times
of the pulses. The time-af-tlight difference of the glass mirror reflection with and without
phantom sample was also estimated by the speetral phase difference metbod (Verhoef et
al., 1985). This resulted in the same estimations of the time differences and therefore these
results are not reported in this section.
The attenuation coefficient at the centre frequency (3.5 MHz) and the attenuation slope
were calculated from the amplitude spectrum of the reflection of the glass mirror with and
without phantom sample, Ppff,z) and Plf,z) respectively:

alf) - 20 [ log10 P /f.z) - log 10 Ppif,z)] I 2d.

In this equation d is the thickness of the phantom sample. The attenuation as a function
of frequency was assumed to be linear. The slope of the least square fit performed on the
data between 2.5 and 5.0 MHz represents the attenuation slope and the value at the centre
frequency is the estimation of the attenuation coefficient.
The backscatter coefficient was calculated from the gated signa), to eliminate the
specular reflections from the front of the phantom and the glass mirror. The gated signa!
was divided into sub-windows of 40 samples length, with 50% overlap, using a double
shaped eosine bell window. The amplitude spectrum of each sub-window was calculated.
Each spectrum was normalized through division by a reference spectrum, to correct for
diffraction effects. After this, the spectra were corrected for the attenuation with the

58
formerly obtained data. The spectra were averaged and for each sample in the averaged
spectrum a least square fit between 2.5 and 5.0 MHz was performed to determine the
backscatter spectrum slope and the backscatter coefficient at the centre frequency. These
two parameters were used to characterize the phantom samples.

REfERENCE
SIGNAL (-20dB) --------------~

A2 (x,y)
ATT~~t~~~~~g ---~'"j------=-:..:-:..:-=.;v:"~----..--'-~
SIGNAL (-20dB) 1 I
1t 1(x,y) I t 2(x,y)

Figure IV.12: Diagram of the signals used in the ultrasound macroscope.

Homogeneous cylindrical phantoms of different compositions were prepared for this

experiment. With the ultrasound tomograph each phantom was measured under the
standard measurement conditions. Because the phantoms are cylindrical symmetrie and
homogeneous, 45 projections were sufficient. From the measured phantoms a 5 mm thick
slice was cut and used in the acoustic macroscope system.
In the reconstructed tomograms a circular ROl was chosen in the centre of the
phantom. In this ROl the mean value of the acoustic parameter was determined.

Results
A series of phantoms with different percentages of n-propanol were measured. The results
of the speed of sound measurements of these phantoms are shown in figure IV.13. The
attenuation coefficient and the attenuation slope versus the percentage n-propanol are
shown in figure IV.l4 and IV.l5 respectively. The measurement of the attenuation is
distorted in the tomographic measurement by refraction and interference, due to the high
speed of sound. These error sourees will be described in the next section. The results of
the scatter measurement are not worth mentioning, because this kind of phantoms hardly
scatters. In the acoustic macroscope system the backscatter was too little, to be measured.
The presented results of the acoustic macroscope system are the mean over 49 samples.
lf the linear regression through the data points is significant (1% ), this line was drawn. The
correlation coefficient 'r' gives an indication over the correctness of the fit. The slope of
the fit is ind.icated with 'a'.

59
 1600 SPEED ~F SOUND (m/s}

1575 ".
r: 0.999
1550 a: 6.7
1525

1500 r:0.986
a: 7.3
1475 L---, - - -. - - - . -- -- . - - - ,- -- . - - - ,- -- ,
0 2 4 6 8 10 12 14 16

% N-PROPANOL

- TOMOGRAPHY - El- · MACROSCOPY

Figure IV.13: Speed of sound versus percentage n-propanol.

3 _00 ATTENUATION COEFFICIENT (dB/cm}

2.30

1.60

0.90
!
0.20 f---<t~_,;,___...__-,L------1;--f---------
-0.50 L----,-------,-- - . - - - - . - -- ,- -- . - - - ,- -- ,
0 2 4 6 8 10 12 14 16

% N-PROPANOL
• TOMOGRAPHY o MACROSCOPY

Figure IV.14: Attenuation coefficient versus percentage n-propanol.

60
 0 _4 ATTENUATION SLOPE (dB/cm MHz)

T T
0
T
0

-0.1 1 •
1
-0.7
I I I
• • I
-1.3
1 I 1 1
-1.8
0 4 8 12 16

% N-PROPANOL

• TOMOGRAPHY 0 MACROSCOPY

Figure IV.lS: Attenuation slope versus percentage n-propanol.

In the phantoms with iron(III)oxide powder added the measured speed of sound varies in
the range from 1489 m/s at 0.1% to 1480 m/s at 4.3%. Therefore, the refraction effect is
smaller than with n-propanol added. The speed of sound as a function of the percentage
iron oxide is shown in tigure IV.l6. The attenuation coefficient at centre frequency and
the attenuation slope we re determined and are shown in tigure IV .17 and IV .18.

1600 SPEED OF SOUND (m/s)

1575

1550

1525

1500

1475
!:'! • 1!1. lli
• ~ .
0 2 3 4 5 6

%IRON OXIDE
• TOMOGRAPHY o MACROSCOPY

Figure IV.16: Speed of sound versus percentage iron(III)oxide.

61
 3 _50 ATTENUATION COEFFICIENT (dB/cm)
b ~
2.80
r: 0.988--- - .."
2.10
a: 0.68 ~--
r: 0.998
1.40 ""-a: 0.64

0 2 3 4 5 6

%IRON OXIDE
- TOMOGRAPHY - -o- - MACROSCOPY

Figure IV.17: Attenuation coefficient versus percentage iron(III)oxide.

ATTENUATION SLOPE (dB/cm MHz)

1.70

1.26
r: 0.988
0.82 a: 0.22
1
0.38 \ r: 0.989
'a: 0.21
-0.06

-0.50 '--~-.--~----,-~--,-~--,--~--,--~---,

0 2 3 4 5 6

%IRON OXIDE
- TOMOGRAPHY - - -o- - -MACROSCOPY

Figure IV.18: Attenuation slope versus percentage iron(III)oxide.

The reflectivity tomograms give quantitative information only in arbitrary units, which are
not equivalent to the backscatter coefficient determined with the acoustic macroscope. To
give an indication of the reflectivity of the iron oxide phantoms, the backscatter coefficient
and the reconstructed value in the reflectivity tornogram are presented in two different
figures . In figure IV.19 the backscatter coefficient at the centre frequency is shown and
in figure IV.20 the reflectivity determined in the tomograms.

62
 BACKSCATTER COEFFICIENT (dB)
-10
T
0

-15 1
T
0
T l

-20
î
ÓH
.L
-25

-30
0 2 3 4 5 6 7 8

%IRON OXIDE

Figure IV.19: Backscatter coefficient measured with the macroscope versus

percentage iron(III)oxide.

REFLECTIVITY (arbitrary units)

0.4

0.3

0.2 T
•
T
•
1 I T
•
1
T
•
1
1
0.1
ITd1
0.0
T ·1
1
-0.1
0 2 3 4 5 6 7 8

%IRON OXIDE

Figure IV.20: Reflectivity measured with the tomograph versus percentage

iron(III)oxide.

Discussion
The results of the quantitative comparison are encouraging. The results indicate that the
measurement of the speed of sound with the ultrasound tomograph is reliable, at least in

63
the measured range. The slopes of the least square fits in tigure IV .13 are al most the same.
The fits show a small bias that could be caused by differences in the temperature of the
water in the tanks. The local speed of sound in the objects is calculated relatively to the
speed of sound in the water. The speed of sound in water is taken to be 1482 m/s at room
temperature and is added to the relative speed of sound values. In fact the speed of sound
in water is temperature-dependent and increases by about 3 m/s per ·c (Greenspan and
Tschiegg, 1959). This causes an error in the values of the reconstructed image. A solution
to eliminate this effect would have been to measure the temperature of the water and to
use the known temperature-dependency in the post-processing of reconstruction program.
The speed of sound is only weakly dependent on the percentage iron oxide. The values
of the speed of sound varied between 1490 m/s in phantoms without iron oxide and 1480
mis in phantoms with 4.3% iron oxide added.
The calculations of the attenuation coefficient at the centre frequency and the
attenuation slope in iron oxide phantoms show good correspondence (figure IV.17 and
IV.l8). The ROl in the tomograms was defined at some distance from the border to avoid
the artifacts at the border. This will surely give a problem in imaging smaller structures.
The values of the attenuation coefficient in phantoms containing n-propanol is almost
zero. This value was also expected. lt was assumed that the unrealistic, negative values of
the attenuation slope in the n-propanol phantoms were a result of distortion of the
measurement by refraction and interference due to the high speed of sound.
The data points of the backscatter coefficient and the reflectivity as a function of the
percentage iron(III)oxide show the same trend. The scattering was found to increase with
the percentage iron(III)oxide, only at low concentrations of scattering iron oxide particles.
It reaches a maximum at about 4% iron oxide and then decreases. This can be explained
as follows: at low concentrations the iron oxide particles behave as incoherent, randomly
distributed scattering particles and single scattering wil! suffice to describe the scattering
process. At higher concentrations of iron oxide particles, multiple scattering occurs and the
scattered ultrasound will interfere destructively.

IV.4.2 Re1ationship between size and quantitative accuracy

The relation between the diameter of a structure and the reconstructed value in that
structure will be described in this subsection. The speed of sound measurement was chosen
to study the relation between size and quantitative accuracy. From the previous subsection
it is clear that the speed of sound measurement is an accurate one.
Four phantoms were manufactured with holes ranging from I mrn to 30 mrn. These
phantoms were used pure and with n-propanol added to increase the speed of sound. To
minimize the effect of diffusing n-propanol out of the phantom into the water-tilled holes,
the contrast chosen was reasonably low (2% n-propanol) and the total number of
projections of one measurement was 80, to reduce the total measurement time. The
experiments were perforrned with the standard conditions, as described in section IV.l.

64
Results
In tigure IV.21 the mean values and the standard deviation determined in the tomograms
of the speed of sound are plotted as a function of the diameter of the structure for the
phantom without and with 2% n-propanol bath. The mean value was determined in a
circular ROl with the size of the hole. The expected speed of sound in the water-tilled
holes is 1482 m/s, the dotted line. This value was taken as the speed of sound in water at
room temperature. The speed of sound in the bulk material of pure agar was 1490 ± 1 m/s
and when 2% n-propanol is added it was 1504 ± 1 mis.

1500 S~EED OF SOUND (m/s}

.L

~
1498

1492 D 2% PROPANOL

Y PURE AGAR
1488

T
bl
1484 I

1480 <.........~;_._.~~~~~~~......_~......._.~_._,

0 5 10 15 20 25 30 35

DIAMETER (mm)

Figure IV.21: Reconstructed speed of sound values as function of the

diameter of the structure.

Discussion
The results show an increasing deviation from the expected value with decreasing diameter
of the structure. This is true of bath types of phantoms. The effect was greater for the
phantom with 2% n-propanol added. The graph of the deviation is steeper if the contrast
between the insertion and the bulk was higher. This corresponds with the results from
unpublished simulations. In spite of the precautionary measures taken to prevent diffusion
of n-propanol into the water, it was still possible that the value in the smallest holes was
influenced a little by the n-propanol. The speed of sound in water is increased by n-
propanol concentrations between 0% and 25% (Nozdrev, 1965). This intensitied the above-
mentioned effect for the phantom with 2% n-propanol added.
An explanation of the described effect is the spatial ]ow-pass character of the
measurement process and of the reconstruction process. The !ow-pass character of the
measurement is caused by the tinite width of the sound beam and therefore depends on the
size and shape of the transducer (Farrell, 1981 ).

65
IV.S Dominant sourees of artifacts influencing the image quality

The spatial resolution, contrast resolution and quantitative accuracy were determined under
optimum conditions. The image quality may be degraded, however, by the introduetion of
a number of artifacts arising from physical phenomena which distort the transmitting sound
wave.

IV.S.l Refraction

One assumption in the foundations of the measurement principles and the reconstruction
theory is that of a straight ray propagation of the sound pulse. Actually this is not correct.
Because of differences in the speed of sound, refraction occurs. This causes an inaccuracy
in the reconstructed image. The influence of refraction on the image quality is the topic
of this section.
Figure IV.22 shows the acoustic rays, refracted at the boundary of a cylindrical object
with a homogeneaus speed of sound, which is higher than that in the surrounding water.
This resembles most of the measurements on phantoms described in this thesis. The error
due to refraction is larger when the distance between the object and the receiving
transducer is larger. Also when the speed of sound in the object increases, the refraction
error increases.
In the description of the error due to refraction, the wave nature of ultrasound is
ignored and instead sound was considered as rays travelling along straight lines. This
model is called geometrical acoustics or ray acoustics, similar to geometrical opties, and
is mathematically justified under certain conditions (Kinsler et al., 1982).
The distortion of the amplitude measurement is the most important, due to much energy
missing the transducer. The smaller the aperture of the receiving transducer, the larger the
error due to refraction. In case of the time-of-flight measurement and the measurement of
the mean frequency downshift, the deviation from the straight path due to refraction is less
important, because it is sufficient when the receiving transducer covers only a part of the
sound beam.

Figure IV.22: Refraction at the boundary of a

cylindrical object.

66
Due to refraction, in echograpbic images the displayed position of certain echoes will not
correspond to the actual locations of the objects that produce those echoes. This artifact
is called geometrie distartion (Robinson et al., 1981; Soetanto and Reid, 1991 ).
The error caused by refraction in ultrasound tomography has been mentioned by several
investigators. Many correcting schemes that use the straight ray reconstruction of the
refractive index or the speed of sound measurements as an input for some iterative
procedures were proposed (Greenleaf et al., 1975; Glover andSharp, 1977, McKinnon and
Bates, 1980; Farrell, 1981, Kim et al., 1984). These methods are often called ray tracing
techniques.
Schomberg (1978) reported a reconstruction metbod based on the more realistic
assumption of the propagation of the sound pulse along the rays with the shortest acoustic
length (according to Fermat's principle of minimal propagation time). In fact this method
is an extension of the well-known algebraic reconstruction method (ART).
The possibility of applying perturbation methods to the refraction problem, as proposed
by Glover and Sharp (1977) was worked out by Norton and Linzer (1982). This method
assumes that the refractive index only deviates from its mean by a small quantity. Using
this, a first order approximation of the ray paths is derived. The expressions for these paths
are then used to obtain useful corrections applicable to both speed of sound and attenuation
tomography. This approach requires neither iteration nor numerical integration of the ray
equation and therefore has a considerable computational advantage over the above-
mentioned iterative methods.
Alternative signa! processing methods have also been used to correct for refraction
errors in attenuation measurements. Crawford and Kak (1982) applied homomorphic
filtering and median filtering of the projections to remove the artifacts. The use of a
combined median and Hamming weighted spatial !ow-pass filter to remove artifacts in
projections, which manifest themselves as noise-spikes, was also studied (Schmitt et al.,
1984a).
Instead of correcting the refraction errors, it has been proposed to avoid these errors
by using large aperture receiving elements that are also phase-insensitive to minimize the
phase cancellation (Klepper et al., 1977; Fitting et al., 1984; Schmitt et al., 1984b).
Two-dimensional matrix arrays are necessary because human tissue is three-dimensionally
refractive (Fitting et al., 1987).
It is difficult to observe an increase in the quality of the experimental results (images)
presented in the literature. McKinnon and Bates (1980) found that if the refractive index
never departs by more than I 0 percent from the average, the simplest method of straight
ray reconstruction is adequate for many practical purposes. In breast tissue the refractive
index varies between 0.95 in fat and 1.05 in parenchymal tissue (Giover and Sharp, 1977).
To derive a formula for the deviation of the straight ray, a simple model was used,
analogous to the denvation by Soetanto and Reid (1991) of the position of a point reflector
in an echogram, when placed behind a cylinder (figure IV.23). This model is also based
on the use of geometrical acoustics.

67
 y

P( X,Y)

Figure IV.23: Analysis of the refraction of an ultrasound ray.

The sound pul se travels from the transmitter T to the boundary of the cylinder P 1. At this
boundary it is refracted and travels to the opposite side P2 , where it is refracted again.
From P 2 the sound pulse travels to the position P. This is not necessarily the position of
the receiving transducer, but has the same x-co-ordinate. When the receiver is in line with
the transmitter, the position of the receiving transduceris (x,y 1).
* The speed of sound outside the cylinder is c 1 and inside the cylinder c2. c 1 < c2 .
* r is the radius of the cylinder.
* h is the distance from the origin 0 to the centre of the cylinder.
* The angle of incidence at P 1 is 0 1. The refractive angle is 0 2 .
* The position of the transmitter is (O,y 1).
By means of equal and similar angles the total angle of refraction 0 is determined as:

0 - 1t -201-~ = 1t -201-(1t -2~) - 2(~-01)

= 2(arcsin( nyl )-arcsin(.::::)) .

r r
The total deviation o is given by:

0 = (x-h)sin0+y 1(1-cos0) .
cos0
Figure IV.24 shows the error o as a function of the distance (Y) from the centre of the
cylinder for different speeds of sound (between 1495 m/s and 1600 m/s) inside the
cylinder. The step size for the speed of sound increase is 15 m/s (~c). The distance
between the object and the receiver is a constant.

68
 The error as a function of the distance (Y) from the centre of the cylinder is plotted
in figure IV.25, for different distances from the object to the receiver (between 2 cm and
10 cm). The speed of sound is 1510 m/s. This graph corresponds to the results publisbed
by Greenleaf et al. (197 5).

4 .0 DEVIATION FROM STRAIGHT RAY (cm)

3.0

2.0

1.0

0.8 0.8 1.0

NORMALIZED POSITION FROM CENTRE y/r

Figure IV .24: Refraction error as a function of the

distance from the centre for different speeds of sound.
c 1 = 1480 m/s; x-h = 6.5 cm; r = 2.5 cm.

4.0 DEVIATION FROM STRAIGHT RAY (cm)

3.0

i'. x- 2 cm
2.0

1.0

0.0
0.0 0.2 0.4 0.8 0.8 1.0

NORMALIZED POSITION FROM CENTRE y/r

Figure IV.25: Refraction error as a function of the

distance from the centre for different positions x of P.
c 1 = 1480 mis; 0_ = 1510 m/s; r = 2.5 cm.

A condusion from figures IV.24 and IV.25 is that the magnitude of the refraction error
due to the distance between the object and the receiving transducer is of less importance.
The speed of sound differences are of much more importance. The speed of sound in
biologica! tissue ranges from about 1475 m/s (fat) to about 1600 mis (muscle) (Chivers
and Parry, 1978), so the modelled refractive indices are in the range that could be expected
in clinical measurements.
Another effect of refraction is due to the curved path of the sound beam. The angle of
incidence of the sound beam on the receiving transducer is not normal and phase

69
cancellation occurs. This effect will distart the amplitude and the rnean frequency
downshift rneasurernent. Phase cancellation is the topic of the next section. In that section
the results of sorne experirnents to illustrate the error caused by refraction and phase
cancellation also will be presented.

IV.5.2 Interference and phase cancellation

In ultrasound tornography, interterenee and phase cancellation are closely related artifact
sources. Interterenee occurs when waves originating frorn different points in the sound
field combine with one another. This produces spatial variations in the intensity and the
frequency of the wave. Interterenee can be caused when a part or parts of the sound bearn
are refracted when travelling through different media or when retlected frorn different
surfaces.
A specific type of interterenee is phase cancellation (Busse et al., 1977). This occurs
when the phasefronts of the ultrasound wave are distorted when arriving at the receiving
piezoelectric transducer. The electrical output of this kind of transducer is proportional to
the rnornentaneous integral of the pressure over the area of the receiving transducer
aperture. Distortions in the phasefront produce a degraded electrical output. Phase
cancellation is therefore an instrurnental effect, related to size, placement and geornetry of
the receiving transducer surface. Variations in the phase of the received ultrasound wave
are usually caused by the fact that the sound wave propagates through media with a
different speed of sound.
Although, these are two different phenornena, the effect on the output of the receiving
transducer is the sarne and therefore they are discussed in one section. Both interterenee
and phase cancellation are rnentioned as a dominant souree of artifacts in ultrasound
tornography. The problern was studied by rneans of a computer sirnulation (Sollie, 1988;
Sollie and Stapper, 1989). In thiS simuiatien two or more pulses are added with a known
time delay and amplitude ratio. The pulses are modelled as sine waves with a Gaussian
envelope.
Frorn the resulting signa! four values are calculated as a function of the time delay:
(1) The maximurn amplitude, which is used in the rneasurernent of the
attenuation coefficient.
(2) The position of the first zero crossing after the signa) exceeds a threshold.
This position is used in the tirne-of-flight rneasurernent.
(3) The centre frequency calculated frorn 112, 1 and 1 112 period after
exceeding the threshold.
(4) The centre frequency calculated frorn the spectrum of the signa!.
The latter two are used to deterrnine the error in the calculation of the attenuation slope.
It was found that large errors occurred in the amplitude rneasurernent and in the
rneasurernent of the centre frequency. The error in the deterrnination of the centre
frequency frorn the spectrum ilid not reduce the errors. Also, the deterrnination frorn more
than half a period increases the errors in the centre frequency deterrnination.
The purpose of this sectien is to investigate experirnentally the effect of phase
cancellation and interterenee on both the individual projection and the reconstruction.

70
Method
To illustrate the magnitude and nature of the phase cancellation artifacts, a phantom with
a circular cylindrical and a triangular cylindrical hole (figure IV.26) was chosen. Because
not the same mould was used for the four phantoms, the layout can differ slightly from
one phantom to the other. The diameter of the circular cylindrical hole was 10 mm and
the side of the triangular cylindrical hole was 15 mm. The composition of the phantom
was agar gel with 2% iron(Ill)oxide and n-propanol. This phantom was manufactured in
four refractive states, by diffusing different percentages of n-propanol. The measurement
was canied out with the standard measurement protocol.

Figure IV.26: Diagram of the

phantom.

To determine the refractive state of the phantoms, the speed of sound was measured in
homogeneous phantoms of the same composition. The proportional difference in speed of
sound between water and the phantom is called the refractive index.
The presence of interterenee and phase cancellation causes obvious distortions of the
pulse-waveferm of the received signa!. Therefore, the pulse-waveferm of a received
ultrasound pulse is recorded every fourth sample of the first projection, by sampling the
received signa! after the automatic gain control amplifier at 20 MHz, with a digital storage
oscilloscope. The digitized waveferm was stored in the personal computer.
To confirm the result of the simulation on the calculation of the centre frequency from
1/2 or 1 period, projections of the duration of 1/2 and 1 period were recorded.

Results
The mean values of the speed of sound, determined in the homogeneous phantoms, are
shown in table IV.1, together with the standard deviations. The refractive index of each
phantom is calculated. The phantoms were numbered from l to 4 with increasing refractive
index.
The intluence of refraction, interterenee and phase cancellation is illustrated by the
phantom images in figures IV.27, IV.28 and IV.29. Speed of sound tomograms of the
phantoms are shown in tigure IV.27. In these tomograms no obvious artifacts are visible.
The tornogram of the phantom withouin-propanol has the Jo west contrast between the bulk
and the water-tilled regions. The average speed of sound of this phantom differs from that
of water by only 1.5 mis (table IV.1). This means a maximum time-of-flight difference of

71
34.1 ns.
Figure IV.28 shows the results of the measurement of the attenuation coefficient. The
first projections of the amplitude measurements are shown on the left side. These were
measured with the transducers moving from the left to the right along the phantom that
was in the same position as depicted in the tomograms. On the rîght side the attenuation
coefficîent tomograms are shown. The tornogram of the least refractive phantom is shown
on the top of the figure and towards the bottom, refraction is increasing. lf there is relative
lîttle refraction, approximated by the phantom without n-propanol, the image quality is
good. However, with increasing refraction, significant errors occur. A region wîth over-
estimation of the attenuation coefficient appears at the borders of the phantoms. At the
phantom-water interfaces an underestimatîon of the attenuatîon appears. In the projections
a small increase of the amplitude is visible at tlus position. The absolute value of this
increase is independent of the refractive state.

(1) (2)

(3) (4)

Figure IV.27: Speed of sound tomograms for four different refractive indices.

72
 No. material speed of refractive
sound (m/s) index

water 1482.0
.. ..
........................................................................................................................................... ..
. . . . . . . . . . . r. . . . . .:. . . . r. . . . . . . . . . . . . . . . . . . . . . T. . . . . . .. . . . . . . . . . . . . . . .
~· ··· ····· · ·········· · ·· · ·······················

~ agar gel + 2% Fe20 3 ~ 1483.5 ~ 0.1

:~·~·~:; :··;;~ ~~:~~

2 ~ 2% n-propanol ~ 1496.1 ~ 1.0

:::·:::~:=··I:::::~~~~~~i~:i~~:~:::::::I··.::::.:. . : :~: : : : : :=: I: : : · · · ~: :~ ·: · ·:. : : : :

Table IV.l: speed of sound of refraction phantoms.

The attenuation slope tomograms presented in tigure IV.29 show poor contrastand artifacts
around the water-tilled regions when the phantoms become more refractive. In tigure IV.30
the pulse wave-forms of the received signals of the leastand the most refractive phantom
are shown, together with the corresponding amplitude spectra. The tirst signa! is recorded
when the sound beam from the transmitter to the receiver is completely outside the
phantom. In the second signa!, the beam is beginning to enter the object. The third signa)
is recorded when the beam travels through both the water-tilled regions. In the fourth
signa!, the beam is beginning to leave the phantom. Finally, in the last signa! the beam is
again travelling completely through water. A distortion of the shape of the pulse is also
recognizable in the spectrum.
The comparison between calculating the attenuation slope from half a period and from
one period shows a slight decrease in image quality in the latter case (tigure IV .31 ). In the
tomograms the orientation is mutually different. This is caused by a rotation of the
phantom during the positioning in the watertank prior to the measurement. The position
of the phantom is not exactly reproducible.

Discussion
The results indicate that ultrasound transmission tomography suffers from artifacts due to
refraction, interterenee and phase cancellation. The effects, predicted in the simulation, are
easy to achieve experimentally in a phantom study. The speed of sound tomograms are
relatively free of artifacts for both weakly and rughly refractive phantoms.
The attenuation coefficient tomograms are greatly affected by artifacts. The geometry
of the refractive phantoms is not clearly recognizable in the tomograms. The value of the
attenuation coefficient inside the water-tilled regions is inaccurate. The negative values are
nonsense. The deviation of the straight ray, due to refraction, causes much energy to miss
the transducer. This causes the overestimation of the attenuation coefficient at water-
phantom interfaces.

73
 The image quality of the attenuation slope tomograms demonstrates a strong
dependenee on the refractivity of the phantom. The shape of the received pulse is
deformed. The amplitude spectra arealso distorted by phase cancellation. This implies that
methods basedon signa] analysis in the frequency domain (Dines and Kak, 1979) also will
be distorted by phase cancellation.

SIGNAL AMPLITUDE

84

SAMPLE NUMBER

(I)

SIGNAL AMPLITUDE

84

SAMPLE NUMBER

(2)

74
 SIGNAL AMPLITUDE

84

SAMPLE NUMBER

(3)

SIGNAL AMPLITUDE

84

SAMPLE NUMBER

(4)

Figure IV.28: Projections ofthe amplitude measurement (Ieft) and attenuation coefficient tomograms
(right) for foor different refràctive indices.

75
 MHZ MHZ

(I) (2)

MHz

(3) (4)

Figure IV.29: Attenuation slope tomograms for four different refractive indices.

76
 _SIGNAL AMPLITUDE M _NORMALIZED AMPLITUDE

2
2
3
3
4
4

to
0.40
TIME (~s) FREQUENCY (MHz)

_SIGNAL AMPLITUDE M _NORMALllED AMPLITUDE

2
2

4 3
6 4

tO

0.40 TIME (~s) FREQUENCY (MHz)

Figure IV .30: Waveforms (left) and corresponding spectra (right) from the received signal at five
different positions along a phantom. top: Least refractive phantom. bottom: Most refractive
phantom.

In the literature some solutions are proposed tö eliminale the artifacts arising from
interterenee and phase cancellation. Large aperture phase-insensitive CdS acousto-electric
receiving transducers are used to image the ultrasonic attenuation (Busse et al., 1977;
Klepper et al., 1977, 1981; Milier et al., 1979). This kind of transduceris only sensitive
to the intensity of the pulse. It was demonstraled that the projections of the attenuation
measurement were substantially better than those measured with a phase-sensitive
transducer.
A disadvantage is that there are no zero crossings in the electrical output. In the case
of the measurement of the mean frequency downshift in the ex perimental tomograph, based
on measuring the duration of one period, the actual implementation is impossible. Also the
implementation of the arrival time detection for time-of-flight measurement would have
to be changed. Finally, the low sensitivity of this kind of transducers (Klepper et al., 1977;
Milier et al., 1979) makes them inappropriate for medica] applications.

77
 MHz

Figure IV .31: Attenuation slope tomograms. left: calculated from measuring half a period. right:
calculated from measuring one period. top: phantom with 2% iron(III)oxide. bottom: phantom with
2% iron(III)oxide and 6% n-propanol.

Another approach is to simulate an array transducer by moving a hydrophone (Jones

et al., 1979; Pan and Liu, 1981). The measured 'miniprofiles' could be processed to obtain
a value for the attenuation, without the phase cancellation errors of a large transducer. This
method resulted in an improved attenuation reconstruction. The approach, however, is very
time-consuming.
The profile migration method (Chenevert et al., 1983) utilizes an array receiver and an
algorithm based on aperture diffraction theory. The array receiver was simulated by a
hydrophone. On the assumption that the object has the same speed of sound as the
surrounding water, the technique displayed slight improvements. However, the tomograms
are still distorted by artifacts due to refraction.
Schrnitt et al. (1984b) used phase-insensitive digital signal processing methods in
combination with a real array transducer to solve the problem of phase cancellation in the
attenuation measurement. A potential problem with the use of an array transducer is the

78
electric and acoustic cross-coupling of the elements.
In spite of this large research effort, no satisfying solution for these artifacts has been
found that could be used in the experimental ultrasound tomograph. The best thing to do
is minirnize it by using a small receiving transducer and correct manually the most obvious
errors in the projections before reconstructing.

IV.6 Genera] discussion

This chapter contains an experimental quantitative evaluation of the imaging features of

the experimental ultrasound tomograph . The four factors considered are the spatial
resolution, the contrast resolution, the quantitative accuracy and the presence of image
distortions and artifacts.
To determine the spatial resolution, the contrast resolution and the quantitative accuracy
the measurements were carried out under optima I conditions. The spatial resolution limit
is of the same order of magnitude as the sample distance. In the experiments this was
about 1.0 - 1.5 nun, with the exception of the reflectivity tomogram. These tomograms
have a very poor spatial resolution . For the attenuation coefficient and the attenuation slope
the spatial resolution is very weakly dependent on the contrast. The speed of sound
tomograms have an increasing spatial resolution with increasing contrast.
The quantitative accuracy is studied by comparing the results of the ultrasound
tomograph with results of a direct measurement technique, called acoustic macroscopy. The
comparison of the values is encouraging. The values of the acoustic properties determined
tomographically match those of the direct measurement technique. The accuracy of the
determined values of the acoustic properties decreases with decreasing size of the structure,
depending on the contrast. This has been shown for the speed of sound measurement. In
the current set-up the properties have their real va lues in structures from 10 mm and larger.
These results concerning spatial resolution, contrast resolution and quantitative accuracy
in ultrasound tomography have never been published as explicitly as is done in this thesis.
When considering the technique as a potentially clinically useful tissue characterization
technique, knowledge of these relationships is necessary, however. It must be noted that
these relationships are dependent on the particular transducers employed, on the tuning of
the measurement device and on the spatial resolution in the reconstruction software.
Probably of more importance for the introduction of the technique as a clinical
technique are the image distortions and artifacts caused by refraction, interference and
phase cancellation. These error sources are illustrated in the last part of this section. Speed
of sound differences cause refraction of the sound beam. The sound does not travel along
straight lines as assumed in the reconstruction theory . The distortion of the amplitude
measurement is the most important. Correcting schemes proposed in the literature are
considered, but none of them provide the ultimate solution for this distortion. Refraction
also causes interference and phase cancellation. These phenomena cause obvious
distortions of the pulse-waveform of the received signal and the spectrum of this signa!.
This affects the attenuation coefficient tomogram and the attenuation slope tomogram .
Observation of the tomograms of the phantom study (figures IV.28 and IV.29) shows the
seriousness of these errors.

79
V Imaging bone-containing tissue structures

Ultrasonic tomographic imaging is a method to obtain quantitative images of different

acoustic properties and is therefore potentially a method to characterize tissues. The
imaging features and the artifacts caused by refraction and interference were studied in
phantom experiments and described in chapter IV. The study described in the present
chapter served to obtain an impression of the applicability of the tomographic methods to
measurements in bone-containing biologica! tissues. The literature on ultrasonic
tomography deals mainly with experiments characterizing soft tissues, because this is in
all probability the most promising application of ultrasound tomography. Most
experimental investigations were performed on the female breast. Imaging the testicles was
also proposedas a significant application (Hiller and Ermert, 1981). In actdition to in vivo
experiments many in vitro experiments were performed on different organs of a variety of
ani mals.
Apart from the parts of the body mentioned above (breast, testicles), almost all parts
of the body contain bone. When imaging e.g. the extremities there are always bones in the
scan plane. The ultrasound beam transrnitted is obstructed by these bones. Only a few
studies described in the literature were performed on structures containing bone (Carson
et al., 1977; Dines et al., 1983). The use of ultrasound tomography would be much more
widespread if bone-containing parts of the body could be imaged. For this reason the
present chapter concerns this topic.
This chapter first deals with the question whether it is possible to image soft tissues if
there is bone in the scan plane. A phantom was manufactured to simulate a bone-
containing structure. This 'bone phantom' was manufactured from Perspex and glycerol
in combination with the soft tissue phantom described in section IV.l.
The second section deals with osteoporosis. Considerable interest is currently focused
on the early detection of osteoporosis in a patient. The currently available techniques to
diagnose osteoporosis measure bone mass or bone density and use ionising radiation.
Ultrasonic properties of bone, however, are related to the bone quality. The measurement
of the speed of sound and the attenuation has been used as a diagnostic technique (Evans
and Tavakoli, 1990). The results are sufficiently encouraging, but the clinical usefulness
of this method has to be established by future research.
Although ultrasound has been used in the diagnosis of osteoporosis, no literature is
known on ultrasound tomography in relation to osteoporosis. Preliminary results of
tomographic measurements on bone tissue will be discussed in the third section.
Finally, it was attempted to measure some partsof the body in vivo. Since ultrasound
transmission tomography is limited to sites that can be scanned over 360 ' without
obstruction by gas-containing structures, the use of ultrasound transmission tomography
is Iimited, apart from the soft tissue parts of the body mentioned above, to the extremities.
Results of measurements on a lower limb and on a middle finger will be given.

80
V.l Measurements on a 'bone phantom'

Previous work on imaging soft tissue through bone with transmiSSJOn ultrasound
tomography was concentrated on the attenuation coefficient (Carson et al., 1977). It was
pointed out in that study that more than adequate signa! energy was transmitted through
the bone to make a reasanabie reconstruction. It should be noted that many questions were
left unanswered. This section describes whether it is possible to image the acoustic
properties of soft tissue accurately, if there are bones in the scan plane.

V.l.l Metbod

A 'bone phantom' for ultrasound measurements was manufactured to enable to measure

under controlled conditions. A comparison of the typical acoustic properties of bone tissue
and phantom materials is given in table V.I. The measured values for bone tissue have a
large variability, depending on the state of preservation of the tissues, variation in
experimental techniques and environmental variables, such as temperature. The acoustic
properties have not been measured systematically and therefore this table is not complete.

tissue or material speed of sound attenuation acoustic

(mis) coefficient* impedance
(dB/ cm) (Mrayl)

cortical bone (man) . 1950 - 3500 . 13 - 19 6- 8

. . ...
...........................................................................................................................................................................................
·--~~~::.~~-~-.?.~~~--~~~-~~~~~---····l·-············~9.?.?................ !.. . . ... . ...... . ... . . . . .!. . . . . . ... . . . . . . . . . . ..

: :~i ~;~ ~ ;~ ~: : l: : : : : : : ~i: :-: : ~:l: : : : : ~:i ~ : :=:l=: :=~:~: : : : : :

::r;~;.~~1;~;;~~~~:·~:J""::_- ~ ~ : : :~: " "1· · : : : : : : ~·~: :-.: : : : r: : : ~:-.~ : :·:· : ·:·
castor oil (C 11 H 100 10) j 1477 ~ 0.95 ~ 1.43
···~·;;~:~~·;··~-~~~~;~;··················r··············~-~-~~··············r················~:;···············r···············;:~················

Table V.l: Typical acoustic properties of bone and phantom matenals as mentioned in the literature.
Sourees of data: Wells, 1969; Weast, 1972; Gosset al., 1978; Kaye and Laby, 1986; Shore et al.,
1986; Rubin et al., 1987.
* Values measured at I MHz unless other frequency mentioned between brackets (in MHz).

81
Polyrnethylrnethacrylate (PMMA, Perspex 1) was chosen as cortical bone equivalent
materiaL PMMA is probably the most widely studied solid polymer in the acoustics
literature and accepted as a reference standard. It is a homogeneaus solid in which the
speed of sound is close to that in cortical bone. Glycerol is used to simulate trabecular
bone.
The phantom designed had a circu\ar cross-section with a diameter of 5 cm. Two sides
were somewhat flattened to approximate the shape of a forearm. The materials used were
agar gel with 2% iron(III)oxide and 4% n-propanol to simulate soft tissue, Perspex tube
to sirnulate cortical bone and glycerol to simulate trabecular bone. The Perspex tubes used
were 10 rnrn and 15 rnrn in outer diameter. The 'cortical' wal! thicknesses were 2.0 mm
and 2.5 mm, respectively. A cross-section of the phantom is shown in tigure V.I. The
Perspex tubes were removable and the phantom could be measured for comparison without
'bones' in the scan plane. The holes were then filled with water. The vertical position of
the scan plane was unirnportant for the reconstruction, because the phantorn was cylindrical
and all axes were parallel.

• 0AGAR GEL

f83PERSPEX
.GLYCEROL

Figure V.l: Diagram of the geometry of the 'bone

phantom'.

The attenuation coefficient of bone increases with a power of the frequency . It was decided
to measure structures containing bone and bone tissue with transducers operating at a
centre frequency of 1 MHz (Panametrics model V303, I!! 1.27 cm), to avoid excessive
attenuation losses of ultrasound energy which render the amplitude of the received pulse
insufficient for detection. Only results of the transmission measurements are reported here,
because the processing electronics of the backscattered signa! was still tuned to the
3.5 MHz previously used in the soft tissue phantom experiments described in chapter IV.
The use of 1 MHz transducers instead of 3.5 MHz transducers theoretically results in a
lower spatial resolution.
The set-up described in chapter 11 was used. The transmitting transducer was energized
by a 280 V electrical block pulse with a duration of half the period time of the 1 MHz
acoustic pulse to be produced. Before the measurements, the transmitter and receiver were

1 Perspex is the trade name of Imperia) Chemical Industries for PMMA.

82
aligned, so that the amplitude received was maxima!. The measurements were carried out
at room temperature. The projections were measured at 85 equispaced angles. The
reconstruction algorithm employed was the direct Fourier inversion algorithm described
in section 11.4.

V.l.2 Results

Figures V.2 and V.3 show the tomograms of the speed of sound, the attenuation coefficient
and the attenuation slope of a 'bone phantom'. Figure V.2 shows a phantom which
contained both Perspex tubes. Figure V.3 shows a phantom of which the smallest Perspex
tube was removed and replaced by water. Due to the large contrast between the Perspex
tube and the soft tissue material, the latter is hardly visible in the tomograms. Rescaling
the tomograms so that the lower values use more grey levels than before results in a
enhancement of the picture of the Perspex tubes. The soft tissue material does not really
become more visible, as a result of the noisy character of the tornogram and therefore this
kind of image processing was omitted.
The mean values and the range of each value were detennined in a region-of-interest
(ROl), to detennine whether the soft tissue phantom material will be distinguishable from
the surrounding water. This ROl was positioned where the phantom should be and the
bones or the water-filled hole were excluded. The mean values and the range of each value
in the Perspex tube and the glycerol were also determined by using an operator-controlled
cursor. These results are shown in table V.2. Reference values of the attenuation slope
were not available.

83
 MHz

Figure V.2: Tomograms of 'bone Figure V.3: Speed of sound (top),

phantom' . Speed of sound (top), attenuation coefficient (middle) and
attenuation coefficient (middle) and attenuation slope tomograms (bottom) of
attenuation slope (bottom). phantom with one 'bone' removed.

84
 material expected two bones one bone
value present present

SPEEp OF SOUND (mis)

mean 1 max. min. mean max. min.

1-----r------l•oooooooooooooooooooo~oooooooooooo o oooooooo~ooooooooooooooooooooo oooooouooooooooooooo~oooooouooooooooooo••!••••••••ooooooooooooo

!. . .
...~~~. ?.~L ..... .........~.?..~.~..............~.?..~.~......!. . .~?..~~..... ~?.~.!...........~.?..~. ~......!. . .~L~.~...) ......~.~.?.?.......
...~:~~?..~~....... .......?~.~~........ .....~?.?~..... j......?.~.~..... j......~.~.?.~..... oooooo~~?.~oooooloooooo?..~.?.~oooo.loooooo~.?.~~......
glycerol 1904 2023 1 2230 1 1829 1990 1 2122 1 1892

ATTENUATION COEFFICIENT (dB/cm)

..
mean ; max.
...
1 mm. mean max . min.
1-----r-----i············--··..···;·····················i····················· ·····················i·····················~·····················

...~~~oo?.~Loo... ....ooooooooooooooooooo... oo·oo··~~:~....oo.Joo.....~:~oo..oo.J...oo..~~:~..oooo. oo.....~J...ooooJ........?.:~oo...ooJ......~~-:?.0000000

Perspex 5.6 l 15.7 l 1.0 6.0 ~ 13.7 ~ 1.5
•oo~•;;·~~~~•;oooooo ooooooooooooooooooooooooooooooooo~;:;oo•ooroooo•~:~oooooorooooo~;:~ooooooo ooooooo~;:~oooooToooooo;•:;ooooooToooo~~-:~ooooooo

Table V.2: Results of quantitative evaluation of 'bone phantom' measurements.

V.1.3 Discussion

The experiments described above demonstrate that tomograms can be obtained if there are
Perspex tubes in the scan plane. The Perspex tubes were imaged with only small artifacts.
Due to the large contrast between the bone material and the soft tissue material, the
tomograms do not depiet clearly the soft tissue material in the surrounding water.
Rescaling of the grey levels does not result in a better depietion of the soft tissue materiaL
The Perspex tubes are sharply visible in the speed of sound tomograms. The size of the
tubes imaged is larger than the true geometrie size. This is caused by the phenomenon
which is known as 'multipath' (Crawford and Kak, 1982). When the beam is near the edge
of a region with a higher speed of sound than its surroundings, the fastest path may indeed
be the path through the region of higher speed of sound. This is demonstrated in figure
V.4. The signals received were recorded after the automatic gain control amplifier by a

85
digital storage oscilloscope. The first signa! was recorded when the beam was travelling
completely through the soft tissue mimicking materiaL In the second signa!, the beam was
beginning to enter the largest Perspex tube. The third signa! was recorded when the
transducers were moved inwardly by two samples(= 0.25 cm) with regard to the position
where signa! 2 was obtained. The fourth signa! was recorded when the beam was
completely travelling through the Perspex tube. The fifth signa! is the blocking window,
which was activated when an acoustic pulse was detected by the receiver. In the figure the
signals are synchronised with the point in time of detecting the received pulse and
activating the blocking window. Therefore, the time of flight cannot be gathered from this
figure.

_SIGNAL AMPLITUDE (V)

-5.5 -3.5 -1.5 0.5 2.5 4.5 6.5

RELATIVE TIME (IJS)

Figure V.4: Received signals (1-4) demonstraling 'multipath' and blocking

window (5).

The small 'blip' in the first signal preceding the received pulse is a contribution from a
small part of the beam travelling through the Perspex tube. In the second signa! the part
of the beam travelling through the Perspex tube has a magnitude sufficient to exceed the
level detector, although the magnitude of the signa! travelling through the agar gel is much
larger. The signa! travelling through the Perspex tube precedes that travelling through the
agar gel because of the higher speed of sound in Perspex. In the third signa! both parts are
comparable in magnitude. In the fourth signa! the predominant pulse travels through the
Perspex tube. It will be clear that 'multipath' will result in a size of the Perspex tube in
the tomograms larger than the true geometrie size.
The attenuation coefficient tomograms depiet an unrealistieally low value inside the
largest tube. In the attenuation eoeffieient tornogram of the phantom with one bone
removed the water-filled hole with a diameter of 10 mm is visible. The border of this
phantom is depieted as more attenuating than its surroundings. On the computer monitor

86
this feature was also visible in the tornogram of the phantom which contains two 'bones'.
This edge enhancement is helpful in demarcating the phantom.
Quantitative evaluation of the tomograms (table V.2) shows that the estimated mean
values of the acoustic properties of the soft tissue material differ from those of water
(1482 m/s, 0 dB/cm, 0 dB/cm MHz). This suggests that soft tissue will be 'visible' in a
scan plane which contains bones. The range of each value that was determined within the
ROl was large. Because of these large variations it is unlikely that details with small
variations in contrast will become detectable.
The values of the speed of sound show a passable agreement with the expected values.
The values of the attenuation coefficient in the agar gel match the expected value. The
values of the attenuation coefficient in Perspex and in glycerol do not show any agreement
with the reference values. The values of the attenuation slope arealso rather unlikely. The
results obtained with the refractive phantoms in chapter IV suggest that refraction and
interference are the main causes of the erroneous results of the 'bone phantom'.
In conclusion it can be stated that bone-simulating Perspex tubes are visible in the
tomograms. Quantitative evaluation shows that soft tissue material can be distinguished
from the surrounding water and that the estimated values of the speed of sound and the
attenuation coefficient are reliable. The estimated values of the acoustic properties in the
bone mimicldng material show large variations or are unrealistic. These results show that
the potential benefits of ultrasound tomography of structures containing bone should not
be overrated.

V.2 Current measurement techniques for osteoporosis

In this subsection it will be explained that osteoporosis is a major health problem and early
detection is important for effective therapy. Simple, safe and fast techniques are required
that should relate to the patient's future fracture risk. The currently available techniques
measure bQne mass and use ionising radiation. Acoustic properties of bone are related to
bone quality, but the clinical usefulness of ultrasound as a diagnostic tooi has to be
established.

V.2.1 Osteoporosis

Osteoporosis is defined as a lower bone mass than might be expected from age and sex
norms and as an increased risk of fractures (Woolf and Dixon, 1988). The development
and maintenance of bone mass depends among others on age, sex, inheritance, physical
activity, nutrition and hormonal state. Peak bone mass is attained at about 35 years. The
density of bone subsequently declines with aging, in both sexes. Another factor affecting
the strength of bone is the internal trabecular architecture. Bone mass measurements and
the rate of loss of bone tissue are useful to assess the risk of osteoporosis.
Osteoporosis is particularly a problem in post-menopausal women. One-third of the
women above the age of 45 suffer from osteoporosis. This causes a lot of injuries,

87
discomfort, pain and inconvenience, and the treatment of the bone injuries and the
rehabilitation afterwards are a significant economie factor. Many treatments have been
investigated and it appears it would be beneficia! if osteoporosis could be diagnosed at an
early stage. An example is the horrnone replacement therapy for women entering the
menopause with a lower than average bone mass (Woolf and Dixon, 1988).
Of the skeletal mass eighty percent consists of compact or cortical bone. It forrns the
outer surface of all bones and is found in the shafts of the limb bones. Spongy or
trabecular bone constitutes twenty percent of the skeletal mass. The centre (medulla) of
bones is made of trabecular bone. lt also fonns the greater part of each vertebral body, the
ends (epiphyses) of the long bones an the heel bone (calcaneum), and is present in the hip
bone (iliac crest). Trabecular bone degrades faster than cortical bone and its measurement
is often considered more important than that of cortical bone mass.

V.2.2 Diagnostic techniques

Quantitative methods of assessment are necessary to diagnose osteoporosis. In table V.3

the methods to diagnose osteoporosis are summarized together with their advantages and
disadvantages and the cammanest measurement site (Woolf and Dixon, 1988; Tothill,
1989).
Four measurement techniques are widely available for measuring bone mass: SPA,
DPA, DXA and QCT. Other techniques are old-fashioned or not yet developed completely.
The methods of table V.3 mostly used are DPA and QCT, because these methods can be
applied to measure at sites of potential fractures. The major disadvantage of all the
methods mentioned in table V.3 is that they use ionising radiation.

88
 technique souree and commonest site disadvantage
effective dose
equivalent advantage

radiogrammetry X-rays midshaft of a only cortical bone

metacarpal of -------------------------
1 mSv the hand simple, fast, and
.........................................1....................................· ········································i .. ·················~~.:~P~.~~!.~~...................
radiographic j X-rays phalanges, distal i only peripheral skeleton;
photo- j ulna, proximal j soft tissue error;
densitometry ~ 1 mSv radius and ~ standardisation required

...................................... !................. ..........,......

single-photon y-rays
~:=::.~:. . ..r:~~~:..:~~=~~:~~i~:.~~
j radius, ulna and j only peripheral bones;
absorptiometry j os calcis j souree must be replaced
(SPA) 0.05 mSv j l several times a year
i r--~~~~-~~d-in~:~~~~i~;--
.................................................. ....... . .................... t .. •••••••••••••••••• .. ···················-=·········••nonooooooonoou•••······························

dual-photon l y-rays j lumbar spine l expensive souree needed;

absorptiometry j j and femoral L-~<:~~-<::':':'~~~~<:~-t~~~---
(DPA) j 0.05 mSv j neck j any part of the skeleton;

=~~~:~~:··j········:::;::~ -!-·-i~::~~~i:~······j--~~~~t~::l~~i···
!
. ci. .r. . r.r------------------------
... ~~·~j~;f ;c~·~;~~. . . . . r. . ~~·~;~;Ïb~d; . . ~~~f!i~~f·:;1::·: ....
· · · · · : ~ :~ :· - !· · -~;~ ~;~ l·····::~~~~:r-I·~~~~f.~;~~~t~:r.~~
. . . . . . =:.~.~~~. . . . . .L. . . .~:.~. .~.~.~. . . . .l.........................................[~.~~.~~.~~.~~.~~.~~.~~.~~.~~.~~.~~.
neutron j neutrons j total skeleton j cyclotron necessary; large
activation j j j radiation dose

analysis I 10 mSv I r-~;~~:~;~~~~f!~:t~~;ï-

Table V.3: Characteristics of methods for bone mass measurements.

89
V.2.3 Ultrasonic assessment of bone

U1trasonic assessment of bone is a fairly recent development. The first interest in the
acoustic properties of bone was stimulated by the attempts to image the brain through the
skull by ultrasound. Measurements of the acoustic properties of the skull were reviewed
by White (1978). An extensive study of the acoustic properties of the human skull, using
relatively low frequencies (range 0.5-2.0 MHz), was published by Fry and Barger (1978).
Later on it was recognized that knowied ge of the acoustic properties of bone could help
to understand bone formation and resorption processes as well as to diagnose various bone
diseases (Adler and Cook, 1975; Yoon and Katz, 1976; André et al., 1980; Menier et al.,
1982).
The elasticity and density of bone are related in a predictabie manner to the speed of
sound. This represents a major difference with the above-mentioned methods for
diagnosing osteoporosis. Those methods measure mineral content or bone mass whereas
ultrasound is used to study elastic properties of bone or bone quality.
The results of the acoustic studies are sufficiently encouraging, but the clinical
usefulness of ultrasound as a diagnostic methad has to be established by future research.
Advantages of ultrasound techniques are that no ionising radiation is involved and they are
relatively inexpensive; both attenuation measurements and speed of sound measurements
can be used.
Langton developed the braadband ultrasonic attenuation (BUA) method. It has been
suggested that ultrasonic attenuation is related to both density and structure of trabecular
bone (Langton et al., 1984). The original system was modified to measure the attenuation
and the speed of sound simultaneously (Langton et al., 1990). The attenuation
measurements are canied out with a broadband pulse applied at the heel bone (calcaneum),
which mainly consists of trabecular bone. A transducer transmits a puise that is received
at the opposite si de. The frequency content of the pul se is stared and at each frequency the
signa! amplitude received is compared with that received without a sample between the
transducers. It was reported that the attenuation slope in the frequency range from 0.2 to
1.0 MHz is greater for normal bone than for osteoporotic bone.
Many studies have been performed on the correlation between BUA values and
different bone mass measurement techniques (Evans and Tavakoli, 1990). This has usually
been done by camparing results obtained at different measurement sites. Although
sametimes good correlations were found, a consensus view of the role of BUA in bone
disease has yet to emerge.
The speed of sound (c) in boneis dependent on theelastic modulus (E) and the density
of the bone (p):

c = JElp .
This identifies a direct relationship between two material properties of bone concerning the
strength and the speed of sound. A large number of measurements of the speed of sound
in vitro and in vivo have been reported (Evans and Tavakoli, 1990).
The next section is coricerned with the question whether it is possible todetermine the
acoustic properties of bone tissue with ultrasound tomography.

90
V.3 Ultrasound tomography measurements on bone in vitro

Ultrasound tomography is limited to sites that can be scanned over 360 ', without
obstruction by gas-containing structures. Therefore ultrasound tomography appears to be
useless to measure the lumbar spine and measurements on bones are limited to the
extremities. Measurements at peripheral sites may not be representative of a site of more
clinical interest such as the trabecular bone of the axial skeleton (Woolf and Dixon, 1988).
With aging the bone demineralization of the extremities continues. Ultrasound
tomographic measurements of these sites might have clinical significanee in evaluating the
quality of the bone at that particular site and predicting future fracture risk.

In this study some measurements were performed to obtain an impression of the possibility
of measuring characteristics of bone tissue. Most of the measurements of ultrasonic
properties of bone described in the literature were made on special preparations of bone,
with flat and polished paraHel sides. The experiments described in this section were with
uncut bone, because this has more clinical relevance.
The femur of a New Zealand white rabbit was chosen because it was readily available
and not too large to introduce it into the experimental set-up. The bone specimen was
obtained from a freshly ki1led rabbitand was stared in water directly afterits removal. The
measurements were performed within 8 hours after sacrifice. There was no direct contact
with air during the period from the excision of the femur to the measurement.
The rabbit femur was about 10 cm long and was measured just below the proximal
base in a transverse direction. The cross-section of the bone at the scan plane used was
almast circular with a eliameter that varied between 8 mm and 10 mm. The cortical wall
thickness varied from 1.0 mm to 2.0 mm. The set-up used was of the same contiguration
as used in the 'bone phantom' experiments described in section V.I.
A remarkable effect was observed in the time-of-flight measurement (speed of sound).
A strong dip appeared in the projection when scanning at a certain angle. The centre
frequency downshift measurement (attenuation slope) had at the same sample positions
either a dip or a top, as a result of distartion of the received pulse. This strong directional
dependenee was not found in the measurement of the amplitude (attenuation
coefficient). This is illustrated in tigure V.5 by two successive projections of each
measurement. It should be noted that this is not an gradual change but occurs from one
projection to the other.

91
 TIME OF FLIGHT TIME OF FLIGHT

84

SAMPLE NUMBER SAMPLE NUMBER

FREQUENCY SHIFT FREQUENCY SHIFT

84 84

SAMPLE NUMBER SAMPLE NUMBER

SIGNAL AMPLITUDE SIGNAL AMPLITUDE

84 84

SAMPLE NUMBER SAMPLE NUMBER

Figure V.S: Transverse projection data of a rabbit bone of time-of-flight (top), centre frequency
downshift (middle) and amplitude measurement (bottom) of two successive projections (left and
right), 3 ' apart.

There is no obvious explanation for the observed effect. There appear to be two possible
explanations. The first is the anisotropy in the speed of sound of the bone (Van Buskirk
et al., 1981). Anisotropy inthespeed of sound was earlier reported in a freshly frozen dog
tibia (Adler and Cook, 1975). lt was estirnated from the projections shown in figure V.5
that the average speed of sound through the bonevaried from 1425 mfs to 1750 mfs.

92
 One of the conditions which must be satisfied by the set of projections to be
reconstructible is that the distribution of the acoustic property is isotropie (section II.l).
Brandenburger et al. (1981) studied the consequences of anisotropy on computed
tomography, focusing on the anisotropy in the attenuation. They concluded that anisotropy
appears to have the potential for corrupting the results of quantitative imaging. Although
successful corrections were demonstrated for special geometries with a known degree and
direction of the anisotropy, general methods are not available.
The second explanation is that the effect is caused by an unknown deviation of the
straight path through the bone. A Jonger time is then needed for the extra distance
travelled. In the literature there is no consensus about the pathway the ultrasound follows
when it travels through a bone in transverse direction (McCartney änd Jeffcott, 1987;
Langton et al., 1991). It appears todependon the shape of the bone and the diameter of
the transducers used.
To investigate if a smaller diameter of the transducers would change the observations
a collimator was mounted on the transmitter and on the receiver resulting in a diameter of
5 mm. The measurements with these smaller transducers yield the same results. Based on
the results that were available we are unable to assess the applicability of either of the two
explanations.
lt will be clear that the sets of projections of the time-of-flight measurement and the
centre frequency downshift measurement were not consistent and a speed of sound
tornogram and an attenuation slope tornogram cannot be reconstructed. The tornogram of
the attenuation coefficient is shown in tigure V.6.

Figure V.6: Attenuation coefficient tornogram of a rabbit

femur.

93
V.4 In vivo measurements of human extremities

lt was also attempted to measure some parts of the body in vivo. The prototype ultrasound
tomograph described in chapter IJ was not designed to be used for in vivo experiments.
The rails which guide the transducer carriers are mounted on top of the platform. The
stepper motors to drive the scanning movements and the conneetion cables are also
mounted on top of the platform. This platform is placed over a water tank (tigure Il.l ).
The subject must be immersed between the two transducers via a circular aperture in the
platform. lt requires a great effort to remain in the same position, without movements,
during a measurement.
The set-up is not optirnized for speed of data acquisition. Only 45 projections were
measured to limit the time needed for a complete measurement. Small movements were
still probable and will influence the results negatively. Braces were mounted to fix the part
of the body as well as possible in order to minirnize these movements. The set-up used
was in the same contiguration as used in the 'bone phantom' experiments described in
section V.l. The scan length was adjusted to the size of the part of the body to be scanned.
The reconstruction algorithm employed was the filtered backprojection algorithm which
proved to give the best results.
The author himself volunteered for the measurements. Measurements of his rniddle
finger, forearm and Jower limb were performed and some of the results will be presented
in this section. The part of the body measured was degreased with alcohol and a thin layer
of acoustic gel was applied to be certain of a gas-free surface.

In tigure V.7 the tomograms of a measurement of the Jower limb are shown. The scan
plane was near the distal heads of the tibia and fibula. The results were obtained after
interactive correction of obvious error spikes in the projection data before reconstruction
and the tomograms were rescaled afterwards. The tomograms are shown without the
common grey scale next to the tomogram, because the quantitative information partly was
lost with rescaling. The results are disappointing. The results of the measurement of the
foreatm, close to the distal heads of the radius and the ulna, are even worse and will not
be presented in this thesis.

94
Figure V.7: Tomograms of a lower limb. Speed of sound (top, left), attenuation coefficient (top,
right) and attenuation slope (bottom, left) and schematic cross-section through the lower limb
(bottom, right) (after Smith et al., 1983).

The tibia and the smaller fibula are visible in the tomograms. The attenuation coefficient
tornogram shows the edge enhancement that was also present in the results of the phantom
measurements. Particularly the speed of sound tornogram and the attenuation slope
tornogram suffer from errors. It is assumed that these errors are caused by interference and
phase cancellation due to the bones in the scan plane.
A middle finger was measured at middle phalanx height. When the finger was scanned
so that the sound pulse travels in the direction from dorsal to palmar, the projection of the

95
time of flight looks like a projection of an object without a bone inside. When scanning
the finger not in the range of projection angles above-mentioned, the bone which has a
higher speed of sound than the soft tissue, is clearly present. This is the same effect that
was observed at the measurements of the rabbit femur. This is illustrated by the projections
in tigure V.8

TIME OF FLIGHT TIME OF FLIGHT

SAMPLE NUMBER SAMPLE NUMBER

FREQUENCY SHIFT FREQUENCY SHIFT

84 84

SAMPLE NUMBER SAMPLE NUMBER

SIGNAL AMPLITUDE SIGNAL AMPLITUDE

SAMPLE NUMBER SAMPLE NUMBER

Figure V.8: Transverse projection data of a finger oftime-of-flight (top), centre frequency downshift
(middle) and amplitude (bottom) measurement of two successive projections (left and right), 6 •
apart.

96
The time-of-flight data and the centre frequency downshift data are inconsistent sets of
projections. These sets are not reconstructible. The tornogram of the attenuation coefficient
is shown in tigure V.9.

Figure V.9: Attenuation coefficient tornogram

of a middle finger.

V.5 Condusion

In addition to measurements on soft tissues ultrasound tomography might be suitable to

image structures containing bone. These bones, however, caused severe distortions in the
qualitative accuracy of the acoustic parameters of the soft tissue in the plane and the
spatial resolution was not as good as in tomograms of only soft tissue samples. This was
demonstraled with measurements of a 'bone phantom'.
Osteoporosis is a major health problem. However, it is possible to prevent post-
menopausal bone loss. Therefore, identification of women at risk of developing
osteoporosis with its attendant fractures is important. Mass screening of that group would
be worthwhile, if a suitable technique could be developed. This technique might be based
on ultrasound.
Some preliminary experiments were performed on a rabbit femur in vitro to obtain an
impression of the possibilities of measuring bone tissue. It was only possible to reconstruct
a tornogram of the attenuation coefficient. The measurement of the time of flight and the
centre frequency downshift result in an inconsistent set of projections. On the basis of the
available results it is not possible to be certain of the cause of this effect. Two
explanations appear possible: anisotropy of the bone or deviations from the straight path
through the bone (or both).
The results of in vivo measurements indicate only that transmission measurements of
an extremity are possible. The bones, however, caused distortions. The current experiments

97
were limited by the non-ergonomie design of the prototype ultrasound tomograph.
Sophisticated design will be necessary to enable measurements without movements of the
part of the body. Distortions of the received signa! by refraction, interterenee and phase
cancellation will still cause severe problems.
On the basis of the results presented in this chapter it can be stated that the potential
benefits of tomographic imaging of structures containing bone using ultrasound should not
be overrated.

98
VI Clinical perspective of ultrasound tomography

The ultimate goal of all medica! research projects in ultrasound transmission tomography
is its clinical application as a quantitative tissue characterization system. This final chapter
deals with the clinical perspeelive of ultrasound tomography. As emerges from the
definition of tissue characterization given in section 1.1, it is essential that the identified
properties correlate with the type or condition of the tissue. The first section deals with the
separability of tissue classes by use of the knowledge of the ultrasonic properties. Pattem
recognition techniques that group data features into classes will be mentioned. The process
of classification will be explained.
The clinical perspective of ultrasound tomography depend inter alia on the accuracy of
the technique and to some extent on the image quality. These aspects were discussed in
a preceding chapter. In this chapter the results will be related to clinical practice. The
clinical acceptability also depends on whether the system is easy to use, the costs of the
system and whether the technique can complement or compete with other, existing
techniques. These aspects will be discussed in section VI.2. Finally, after some
recommendations, the general condusion will be presented.

VI.l Tissue classification using acoustic parameters

An advantage of ultrasound tomography is that a variety of ultrasonic properties of a tissue

can be measured simultaneously. Each tornogram depiets a different property of the tissue.
The combination of these tomograms, giving quantitative information, can be used to
classify tissues. In the literature the term 'pattern recognition' is used for techniques that
classify data in two or more groups.
Using a pattem recognition technique, the results of a multi-property measurement can
be presented more effectively. Clinical diagnosis will be easier and even diagnostic
information that is not appreciable in the separate images rnight be obtained. If a
sufficiently high specificity and sensitivity could be obtained, the realization of mass
screening systems for certain disease conditions will also be possible.
In the literature several projects have been described in which pattem recognition
techniques with ultrasonic features were used to classify breast tissue (Greenleaf and Bahn,
1981; Good et al., 1982; Finette et al., 1983; Scherzinger et al., 1989). Scherzinger and co-
workers used quantitative linear discriminant analysis (Lachenbruch, 1975) on data
obtained by ultrasound tomography to classify cancer in the breast. This method formulates
decision rules for classifying data from linear combinations of the measured properties
using training sets. lt appeared that the speed of sound in malignant tissue compared with
normal tissue and the attenuation coefficient of the lesion compared with the attenuation
coefficient of the breast as a whole, discriminate between cancer, solid benign masses and
cysts.
These facts were the reason why a student in our research group (Lambregts, 1992)

99
implemented a classification scheme that was employed on tomograms obtained with
simulated data and on tomograms from a phantom experiment.
The first step in the classification process is to extract features. Features are quantitative
measures of information. In the special case of the tomographic measurement technique
described in thls thesis the features are the speed of sound, the attenuation coefficient, the
attenuation slope and the reflectivity. These four features can be combinedintoa feature
vector that spans a four-dimensional feature space. By partitioning the space into regions
which enclose veetors of only one of the classes, classification of tissue might be
performed.
A requirement of a classification scheme is that the classification errors are as small
as possible and known. Two kinds of classification methods exist. Supervised classification
methods (Fukunaga, 1990) use a training set which comprises features with known class
memhership to partition the feature space into classes. A new feature is grouped in the
class to which it most probably belongs. Unsupervised cluster analysis (Fukunaga, 1990)
empirically determines the classes from the data features. Unsupervised methods need no
'a priori' class information.
Lambregts (1992) measured a phantom of agar gel with an insert of agar gel with 8%
n-propanol and I% iron oxide, an insert of agar gel with 2% n-propanol and 4% iron oxide
and a water-filled hole. He applied a linear discriminant analysis on a training set of
vectors. This resulted in two significant features, composed of a linear combination of the
measured properties. A classification scheme based on the linear Bayes decision rule
(Fukunaga, 1990) discriminated with a correctness of 94%.
It is not certain in advance that all features discriminate between different classes. A
measure of the separability of tissue classes with the features used is the Hotelling trace
(Fukunaga, 1990). Features have to be selected to maximize this quantity in order to obtain
optimum separation. Figure VI.! shows the Hotelling trace (J) for feature veetors
consisting of permutations of the four properties measured in the phantom experiment:
speed of sound (c), attenuation coefficient (a), attenuation slope (d) and reflectivity (cr).
Two discrimination tasks are considered:
(I) agar with 2% n-propanol and 4% iron oxide versus surrounding pure agar (o) and
(2) agar with 8% n-propanol and 1% iron oxide versus pure agar (~).
It is apparent from figure VI. I that the attenuation coefficient and the reflectivity provide
the largest separability for task I. For the second task the speed of sound provides the
largest separability. The attenuation slope does not contribute to the discrimination of the
different classes.

100
 80 I I
I I t:.
I I
50 I I t:.
I t:. I t:.
t:. I t:. t:. I t:.
40 I I
I I
I I
...., I I
30 I I
0 I 0 0 0 I 0 0 0 0
0 0 0 0
I I
20 I I
I I
I I
I I
10 I I
I I
I I
0
c a d a ca cd ca ad oo ad cad co a cd a ad a coda

Figure VI.l: Hotelling trace for permutations of the four measured properties
(Lambregts, 1992). o: task I, ó: task 2.

These results are encouraging, although a conclusive statement concerning the applicability
of pattem recognition in combination with ultrasound tomography and the most
discriminating features should only be made after more research. As stated by Lambregts
( 1992) further research is necessary because of Jack of consistent quantitative information
on the acoustic parameters in biologica! tissues and the quality degradation of the
tomograms by artifacts.

VI.2 Clinical applicability of ultrasound tomography

From the project described in this thesis and other research projects described in the
literature it is clear that ultrasound tomography is not suitable for cross-sectional imaging
of the whole body. Ultrasound transmission tomography requires a geometry in which
ultrasound can be transmitted from many directions, covering 360 • around the site of
examination.
Since gas obstructs ultrasound propagation completely, transmission ultrasound
tomography is limited to anatomie sites where this djsrurbjng factor is not present. Among
the sites satisfying both conditions are the female breast, the male genitalia, the extremities
and the head.

101
Examination of the breast
Ultrasound tomography was focused first on detection and diagnosis of caoeer in the breast
(Glover, 1977; Greenleaf et al., 1978; Carson et al., 1981; Koch et al., 1983; Schreiman
et al., 1984). The properties under investigation were the speed of sound and the
attenuation coefficient.
Conventional echograpbic imaging techniques have long been used in the detection and
diagnosis of lesions in the breast. These techniques provide essentially qualitative images
of tissue interfaces and scattering. The availability of high-quality equipment has rapidly
improved the clinical accuracy of detection in the last few years.
Ultrasound tomography provides quantitative images of the measured parameters that
can be analyzed numerically. Lesionsin the breast are generally distinguished by a higher
speed of sound relative to the embedding tissue (table 1.2). It appears that the attenuation
coefficient is less characteristic of a given tissue type. In fatty breasts, where the average
speed of sound is relatively low, lesions show up very clearly with ultrasound tomography.
The amount of fat increases after puberty and by the time of menopause fat is the major
volumetrie component of the breast. Menopausal women are also the highest risk group
for breast cancer. However, none of parameters is very specific toa given tissue type and
a definite tissue characterization is frequently difficult. The variability in the acoustic
parameters of 'normal tissue' between women is substantial. Using a linear discriminant
analysis on speed of sound and attenuation data obtained by ultrasound tomography
Scherzinger et al. (1989) concluded that a sensiti vity and specificity to malignant and
benign lesions of approximately 85% is obtained. This is rather high, but not equal to the
performance of X-ray mammography.
A disadvantage of imaging the breast with ultrasqund tomography is that the patient
lies face down on an examinatien table above a water tank and one breast is immersed
between the transducers. This positioning is necessary to image close to the chest wal! to
detect lesions deep within the breast. For surgery the patient lies on her back and the
internal geometrie position of the tissues in the breast is quite different. This makes it
difficult for the surgeon to correlate images precisely with tissues.
As a rule, X-ray mammography is used to examine the breast and ultrasound
echography is used as a supplemental technique. Recently colour Doppier was used to
image tumour neovascularity (Adler et al., 1990; Cosgrove et al., 1990). Comprehensive
clinical studies are required to establish the role of this Doppier technology for the
assessment of early breast disease.
Combined use of X-ray mammography, B-mode imaging and colour Doppier leads to
increased accuracy in the detection and characterisation of lesions in the breast. No further
diagnostic procedure is necessary as a rule. After detection of a lesion biopsy is generally
performed. The overlap of the ranges of the acoustic properties of different tissue types
and the limited overall accuracy of ultrasound tomography make it unlikely that biopsy can
be avoided. Consequently, the intrinsically quantitative character of ultrasound tomography
loses part of its value. The use of non-ionising radiation such as ultrasound offers a safe
method for mass screening. High-risk patients can be examined repeatedly without the risk
of X-ray radiation. However, the level of radiation has been decreased in modern X-ray
mammographic equipment in recent years, obviously reducing one of the advantages of
ultrasound tomography. Considering these results, it is clear that ultrasound tomography

102
is not adequate to assume a major role in early detection and diagnosis of breast cancer.

Bone quality measurement

Another important application of ultrasound tomography might be the diagnosis of
demineralization of bone discussed in chapter V. Osteoporosis is a major health problem.
Many treatments have been investigated. It appears that therapy can be effective if
osteoporosis could be diagnosed in an early stage. No existing bone mass measurement
technique is ideal (table V.3).
Ultrasound techniques appear to be useful diagnostically but clinical applicability bas
to be established by future research. The ultrasound techniques for the diagnosis of bone
disease as known from the literature are split into two categories: speed of sound
measurements and attenuation measurements (Evans and Tavakoli, 1990). No literature is
known about ultrasound tomography in relation to osteoporosis.
An advantage of ultrasound techniques in general is that no ionising radiation is used.
The acoustic properties are related to bone quality. An disadvantage of ultrasound
tomography is that only peripheral sites can be measured. Ultrasound propagation is
obstructed by gas containing structures. Measurements of the trabecular bone of the lumbar
spine which is of clinical interest, appears to be impossible.
Prelirninary results in a rabbit femur in vitro (chapter V) indicate that the place of
ultrasound tomographic examination of bone will be limited. It was only possible to
reconstruct a tornogram of the attenuation coefficient. The projection data of the time-of-
flight measurement and the centre frequency downshift measurement were inconsistent. It
was not possible to give an explanation for this distartion using the available results.

General remarks
The tomograms are disturbed severely by refraction of the ultrasound beam at interfaces
between tissues with different speeds of sound. These distortions were discussed in chapter
IV of this ·thesis. lt appears to the author that these image distortions are the major
lirnitation of the clinical usefulness of ultrasound tomography. In spite of research interest
in reduction of the artifacts no satisfactory solution has been found. The proposed
correction methods cause only very slight improvements of the reconstructions.
To use the technique as a quantitative technique the quantitative accuracy has to be
high. Ultrasound tomography can offer high quantitative accuracy, as described in chapter
IV, but not in small structures. Smalllesions are often of more clinical interest than large
homogeneaus ones. It can be concluded that impravement of the quantitative accuracy is
desirabie and necessary before introduetion of the technique as a clinical technique.
A more practical disadvantage is that the body part under examination must be
suspended in a water tank between the two transducers. Medica! doctors, because of the
risk of bacteriological infection show restraint in using water tanks in clinical practice. The
first contact-free lithotripters also used large water tanks but these were avoided soon.
Examples exist of breast scanners using a flexible plastic bag for ultrasound coupling to
the patient, but this is not very useful. No research aimed at a practical solution of this
disadvantage is known to the author. It appears necessary that a successful salution should

103
be found before any clinical application.
Ultrasound is a safe technique. This is an advantage in clinical application. Other
techniques use harmful radiation and may not be used repeatedly. The necessary safety-
measures are expensive.
An important advantage of ultrasound tomography and ultrasound equipment in,general
is that it is relatively cheap. This is one of the reasons why conventional ultrasound
equipment is widely used in clinical practice beside techniques with better imaging
properties such as MRI.
Ultrasound tomography using speed of sound could be clinically useful as a tooi for
correction of computer-aided compound scan images (Jago and Whittingham, 1992). This
method uses the quantitative values of the speed of sound measurement, but the final
reflection tomograms are not quantitative.
Because of the above-mentioned disadvantages it will be clear that ultrasound
tomography will never replace one of the existing techniques. Ultrasound tomography
might be used as a supplemental technique for a specific clinical application. Consictering
all the aspects mentioned above, the future of ultrasound tomography remains unknown.

VI.3 Recommendations

Future research in ultrasound tomography should be aimed at a clear clinical application.

Advantages and disadvantages of the metbod were described in this thesis. Within the
constraints of the metbod a fast and convenient ultrasound tomography system should be
designed that is optimally adapted to that clinical application. The measurement of the
relevant acoustic parameters must be implemented utilizing the most adequate methods.
Clinical trials should be performed with such a redesigned system to assess the true value
of ultrasound tomography.
In constructing a new system the use of digitization hardware to sample the received
signa! need not be avoided. The improvements of sufficiently low-cost digitization boards,
which can be plugged into the PC, forthcoming in the next few years allow redesign of the
measuring electronics. Improvements in signa! processing may be expected, particularly
in the measurement of the reflectivity (chapter lil).
A limitation of the system used in this study was the long scanning time. From a
clinical point of view it is important to reduce the examinatien time in order to minimize
discomfort to the patient and to avoid artifacts due to motion. The use of linear array
transdoeers instead of single-element transducers allows electronically rather than
mechanically lateral scanning, resulting in shorter scanning times.
A worthwhile dèvelopment is the use of ultrasound transmission tomography combined
with computer-airled compound scanning (Jago and Whittingham, 1992). The speed of
sound tomograms were used to correct the B-mode images prior to superimposirig those
images. This may be an important application of transmission tomography, since less
accuracy is required for significant corrections to be made.

104
VI.4 General conciosion

This study describes the assessment of ultrasound tomography as a technique for

quantitative tissue characterization. A prototype ultrasound transmission tomograph was
extended with the measurement and analysis of the backscattered signal. This measurement
is performed simultaneously with the measurement of the time of flight, the amplitude of
the received pulse and the centre frequency of the received putse. This results in
tomograms of the local reflectivity, the local speed of sound, the local attenuation
coefficient and the local slope of the attenuation coefficient as a function of frequency,
respecti vely.
In this thesis the imaging features of the system were assessed. The spatial resolution,
the contrast resolution and the quantitative accuracy were determined in phantom
experiments. These results regarding the imaging capabilities have never been published
as explicitly as in this thesis.
The image quality is degraded by artifacts due to refraction, interference and phase
cancellation. Because of the differences in !ocal speed of sound the sound beam does not
travel along straight rays, as was assumed in the reconstruction algorithms. This was
demonstrated by the dependenee of the image quality on the refractive index of the object.
These artifacts proved to be a major problem in ultrasound tomography.
Application of ultrasound tomography is limited to only a few organs. It was hoped that
ultrasound tomography might be used to diagnose demineralization of bone. Preliminary
results indicate that ultrasound tomography is not very useful in this application. Si nee high
accuracy and image quality are necessary for clinical use, the technique is not adequate to
assume a role into the forefront of clinical diagnostic instrumentation.
In condusion it can be stated that ultrasound tomography was implemented in a
prototype, measuring four acoustic properties simultaneously. Because of limited quality
and accuracy of the tomograms a major clinical success and commercialization of the
method have not yet been achieved. A break-through is not expected and the future of
ultrasound tomography remains unknown.

105
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Summary

This thesis deals with the assessment of ultrasound tomography. The imaging features
of a prototype ultrasound tomograph are described. In this set-up, transmission ultrasound
tomography and reflection ultrasound tomography are combined. Finally, the perspectives
to use ultrasound tomography as a technique for quantitative tissue characterization are
discussed.

Chapter I

In this chapter a short survey of the history of transmission techniques in diagnostic

ultrasound is given. In the early seventies transmission ultrasound computerized
tomography is developed. This technique appears to be very useful for quantitative tissue
characterization. Ultrasound tomography is not restricted to systems using the transmission
of the ultrasonic beam. Ultrasound tomography in the reileetion mode is described shortly
after the development of transmission tomography. Another ultrasound tissue
characterization technique being researched is quantitative B-mode imaging, using
conventional echograms. Transmission tomography, reflection tomography and quantitative
B-mode imaging techniques are discussed and publisbed results are summarized.
Because of a growing interest in quantitative tissue characterization different techniques
are developed outside the range of ultrasound. These methods are mentioned shortly.
To understand the complex interactions between ultrasound and biologica! tissue it is
essential to know more about the physics of ultrasound. An ultrasound wave is atienuated,
primarily as a result of absorption and scattering, when it passes through tissue. The
attenuation is frequency-dependent.
The scope of the study is a continuation of the research done by Gert Sollie (1988).
The aim is to further develop an existing prototype ultrasound tomograph and to
investigate whether the system cao be used for quantitative tissue characterization.
To this end, an experimental quantitative evaluation of the imaging features of the
system is performed.

Chapter 11

In Chapter 11 the measurement techniques used and the measurement dëvice are
described. The principles of computerized tomography, concentrating on ultrasound
tomography, are explained. The goal of computerized tomography is to make a cross-
sectional image of an object. To be able to reconstruct such a cross-sectional image, a set
of one-dimensional data, giving information about an acoustic property óf the object, is
necessary. These data are obtained along a linear scan of the object. These scans are taken
at a variabie number of angles, equally divided over 180 •. The reconstruction is done

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using one of the available reconstruction aJgorithms.
A personal computer and a single chip microcontroller are used for the control of the
measuring device. The PC is also used to reconstruct the tomograms. The set-up provides
us with four acoustic parameters:
the speed of sound,
the attenuation coefficient,
the attenuation slope and
the reflectivity.
These parameters are determined respectively by the measurement of:
the time of flight,
the amplitude of the received sound pulse,
the downshift of the centre frequency and
the backscattered power.
Two reconstruction algorithms, both based on the 'Centra! Section Theorem', are
descri bed: the filtered backprojection algorithm and the direct Fourier inversion algorithm.
The latteroneis implemented using a Hardey transfarm insteadof the well-known Fourier
transform. The Hardey transform is faster and the forward transform and the inverse
transform are symmetrical operations.

Chapter 111

Chapter 111 camprises a detailed discussion of the measurement and the processing of the
backscartered signa!. The backscatter processing circuit integrates the RF-signa! in time
after the signa! is rectified and !ow-pass filtered . The measurement is performed
simultaneously with the other three measurements. The measured data is called integrated
backscatter and is a measure of the backscartered power. The key difference from other
methods described in the literature is that digitizing the RF-signa! is not necessary.
After reconstruction, a tornogram of the reflectivity distribution results. Absolute
calibration of the values of the integrated backscatter using a perfect reflector as reference
cannot be obtained with the tomographic system. For this reason the reconstructed
reflectivity va)ues are in arbitrary units.
The results of some phantom experiments demonstrate the feasibility of the method.
The tomograms show that the geometry of the intemal structure of the phantoms is
represented clearly.

Chapter IV

Chapter IV deals with the assessment of the tomograms obtained with the prototype
ultrasound tomogi:aph. The imaging features considered the most important are spatiaJ
resolution, contrast resolution and quantitative accuracy. These features were studied
in phantom experiments which repcesent the optimum conditions.
The tissue-mimicking phantoms are made of agar-agar gel, in which a n-propanol

124
concentration delennines the speed of sound. The attenuation and scattering properties can
be influenced by adding iron(III)oxide powder during manufacturing. The acoustic
properties are chosen so that they resembie those of biologica! tissues. The geometry of
the phantoms is known.
The resolution limit of the ex perimental ultrasound tomograph is about 1.0 - 1.5 mm,
in case of the speed of sound, the attenuation coefficient and the attenuation slope
measurement. Structures smaller than 6.0 mm are too small to become visible in the
reflectivity tomograms. The spatial resolution is contrast-dependent A description of the
contrast resolution is given using contrast-detail visibility diagrams.
The values of the acoustic properties depicted in the tomograms are compared with
those measured with a direct measuring technique (ultrasound macroscopy) to deterrnine
the quantitative accuracy. The results of the quantitative comparison are encouraging. The
results indicate that the tomographic measurements are reliable, at least in the range
measured.
A separate experiment investigates the relation between the diameter of a structure and
the reconstructed value in that structure. The accuracy of the detennined values of the
acoustic properties decreases with decreasing si ze of the structure. For the speed of sound
in a structure it has been shown that it has its real values in structures of 10 mm and
larger. An explanation of this effect is the low-pass character of the measurement process
and of the reconstruction process.
Important for the introduetion of the technique for clinical applications are the image
distortions and artifacts caused by refraction, interference and phase cancellation. The
errors caused by these sourees are illustrated by phantom experiments. The speed of sound
tomograms are relatively free of artifacts for both weakly and highly refractive phantoms.
The attenuation coefficient and attenuation slope tomograms are greatly affected by
artifacts. The geometry of the refractive phantoms is not clearly recognizable.
The effects of interference and phase cancellation, as predicted in a computer
simulation, are confinned experimentally. These phenomena cause a deformation of the
received wavefarms and also of the amplitude spectra of the received pulses. This implies
that methods based on analysis in the frequency domain also will be distorted by these
sourees of error.
Correcting sehernes proposed in the literature are çonsidered, but none of them provides
the ultimate salution for these distortions.

Chapter V

In this chapter measurements of bone-containing tissue structures and bone tissue were
discussed. For ergonomie reasans theset-upis unfit for in vivo experiments and therefore
mainly in vitro experiments were performed.
The first aspect discussed in this chapter is the question whether it is possible to image
soft tissue if there is bone in the scan plane. A 'bone phantom' was manufactured from
Perspex and glycerol in combination with agar gel to simulate a bone-containing structure.
Quantitative evaluation of the tomograms shows that the speed of sound tornogram is a

125
reliable one. The attenuation coefficient in agar gel matches the expected value. The
attenuation coefficient in the bone-simulating material does not show any agreement with
the expected value. The values of the attenuation slope also are rather unlikely.
Demineralization of bone (osteoporosis) is a major health problem and early detection
is important for effective therapy. Although ultrasonic assessment of bone appeared to be
useful as a diagnostic technique, no literature is known on ultrasound tomography in
relation to osteoporosis. A tomographic measurement technique is limited to sites that can
be scanned over 360 ° without obstruction by gas-containing structures. Therefore
ultrasound tomography might only be useful in evaluating the quality of bone in the
extremities.
The femur of a rabbit was measured in vitro to obtain an impression of the possibility
of measuring characteristics of bone tissue. The set of projections of the time-of-flight
measurement and the centre frequency downshift measurement were not consistent and a
speed of sound tornogram and an attenuation slope tornogram could not be reconstructed.
Only the attenuation coefficient tornogram depicted the cross-section of the bone.
Finally the results of some in vivo measurements on a finger, a forearm and a lower
!i mb were presented.

Chapter VI

The final chapter describes the clinical perspective of ultrasound tomography. The
objective of all research projects in medica! ultrasound tomography is its clinical
application as a quantitative tissue characterization technique. Therefore it is essential that
the acoustic properties identified correlate with the type or condition of tissue.
Pattem recognition techniques are explained briefly. These techniques classify data
into two or more groups using discriminating features . The four features measured with
the prototype ultrasound tomograph are the speed of sound, the attenuation coefficient, the
slope of attenuation as a function of the frequency and the reflectivity. Before
classification, the feature space is reduced to a minimal dimensionality, spanned by the
most discriminating features. Due to a Jack of consistent quantitative information on the
acoustic properties of biologica! tissues and the poor quality of the tomograms, further
research is necessary before ultrasound tomography can be used in a combination with
pattem recognition techniques.
Ultrasound tomography is only suitable for parts of the body that can be examined
from 360 o around and which do not contain gas. One of these parts is the female breast.
Ultrasound tomography was focused first on the early detection and diagnosis of breast
cancer. From the results publisbed in the literature it was concluded that the sensitivity
and specificity of ultrasound tomography cannot compete at this moment with those of X-
ray mammography combined with echographic B-mode imaging.
An important application of ultrasound tomography rnight be the diagnosis of
demineralization of bone (osteoporosis). Although the measurement of the speed of sound
and of the attenuation bas been used in the diagnosis of osteoporosis, no literature is
known about ultrasound tomography in relation to this application. Preliminary results of

126
tomographic measurements on a rabbit femur in vitro, and on a human finger and lower
limb in vivo were presented. These results show that the benefits of ultrasound
tomographic imaging in relation to osteoporosis should not be overrated.
Some recommendations are given based on the work in this thesis and the present
knowledge of ultrasound tomography. A clear clinical application needs to be known to
guide further research in ultrasound tomography. A fast and convenient system has to be
redesigned dedicated to that specific clinical application.
Finally the general condusion is given. It states that because of poor quality and
accuracy of the tomograms a major clinical success and commercialization of the method
have not yet been achieved.

127
Samenvatting

Dit proefschrift bevat een studie van ultrasone tomografie. De afbeeld.ingseigenschappen

van een prototype van een ultrasone tornograaf zijn onderzocht. In het prototype is een
transrrussie-meting gecombineerd met een reflectie-meting. De mogelijkheden voor het
gebruik als methode voor kwantitatieve weefsel-karakterisering worden beschouwd.

Hoofdstuk I

In dit hoofdstuk wordt een kort historisch overzicht gegeven van de ontwikkeling van
transmissie technieken bij diagnostische methoden die gebruik maken van ultrageluid. In
het begin van de 70'er jaren wordt ultrasone transmissie tomografie geïntroduceerd.
Deze methode lijkt veelbelovend voor het gebruik als kwantitatieve weefsel-
karakteriseringstechniek. Kort na de introductie van ultrasone transmissie tomografie wordt
ultrasone reflectie tomografie ontwikkeld. Ook wordt er onderzoek verricht naar de
kwantitatieve informatie in de conventionele B-mode afbeelding (echogram). Voor
transffilSSie tomografie, reflectie tomografie en de kwantitatieve B-mode
afbeeldingsmethode worden in de literatuur beschreven technieken en resultaten
samengevat.
Ook buiten het gebied van het ultrageluid worden er technieken ontwikkeld, die voor
kwantitatieve weefselkarakterisering gebruikt worden. Deze technieken worden in het kort
besproken.
Voor een beter begrip van de wisselwerking tussen ultrageluid en biologisch weefsel
worden de basis begrippen van de fysika van medisch ultrageluid besproken. Wanneer
ultrageluid voortplant door weefsel, wordt het gedempt. Deze demping wordt voornamelijk
veroorzaakt door absorptie en door scattering. Beide zijn afhankelijk van de frekwentie van
het gebruikte ultrageluid.
Het hoofdstuk besluit met een beschrijving van het kader waarbinnen het onderzoek is
uitgevoerd. De studie is een voortzetting van een eerder promotie-onderzoek, verricht door
Gert Sollie (1988). Het doel is het bestaande prototype uit te breiden en de
karakteristieken van de afbeeldingen vast te leggen, om zodoende de mogelijkheden
voor kwantitatieve weefselkarakterisering te beschouwen.

Hoofdstuk 11

Hoofdstuk 11 beschrijft de meetmethoden en de gerealiseerde meetops telling. De principes

van computer tomografie worden besproken. De meetgegevens worden verzameld
gedurende een lineaire scan van een voorwerp. Dit wordt herhaald onder een groot aantal
hoeken, verdeeld over 180 graden. Uit de meetgegevens kan door middel van een geschikt
reconstructie algoritme een twee-dimensionale afbeelding van de gemeten doorsnede door

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het voorwerp worden berekend.
De gerealiseerde opstelling wordt door een PC en een micro-processor bestuurd. De PC
wordt ook gebruikt voor de reconstructie van het tomogram. In de opstelling is de meting
van vier akoestische parameters geïmplementeerd :
de looptijd van de geluidspuls,
de amplitude van de ontvangen geluidspuls,
de centrum frekwentie van de ontvangen geluidspuls en
een maat voor het gescatterde vermogen.
Hieruit worden tornogrammen gereconstrueerd waarin de contrast gevende parameter
respectievelijk is:
de geluidsnelheid,
de dempingscoëfficiënt,
de dempingshelling en
de retlektiviteit.
De dempingshelling zegt iets over de frekwentieafhankelijkheid van de demping. De
metingen worden afzonderlijk besproken.
Twee reconstructie algoritmen worden besproken: het gefilterde terugprojectie algoritme
en de directe Fourier inversie algoritme. Beiden zijn gebaseerd op het 'Centrale Sectie
Theorema'. Het directe Fourier inversie algoritme is geïmplementeerd met een Hardey
transformatie in plaats van een Fourier transformatie. Deze transformatie is sneller en voor
het heen- en terug-transformeren kan hetzelfde algoritme worden gebruikt.

Hoofdstuk 111

In hoofdstuk m wordt in meer detail de meting en analyse van het reflektie signaal
besproken. Dit gereilekteerde hoogfrekwente signaal wordt gelijkgericht en de omhullende
wordt geïntegreerd met analoge elektronica. De meting wordt tegelijkertijd met de meting
van de andere drie akoestische parameters uitgevoerd. De gemeten waarde wordt
'integrated backscatter' genoemd en is een maat voor het gescatterde vermogen. Een
belangrijk verschil met andere in de literatuur beschreven methoden is dat digitalisatie van
het hoogfrekwente signaal niet nodig is.
Na reconstructie wordt een afbeelding van de lokale retlektiviteit verkregen. Omdat
absolute kalibratie niet mogelijk is, is het tornogram in arbitraire eenheden weergegeven.
Aan het einde van het hoofdstuk worden de resultaten van enkele metingen aan
weefselfantomen getoond. De metingen tonen aan dat het mogelijk is om geometrisch
correcte afbeeldingen van de fantomen te maken.

Hoofdstuk IV

De kwaliteit van de tornogrammen wordt bestudeerd in hoofdstuk IV. Als meest

belangrijke parameters voor beeldkwaliteit worden spatiële resolutie, contrast resolutie
en kwantitatieve nauwkeurigheid besproken. Deze eigenschappen worden onder zo

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optimaal mogelijke omstandigheden bestudeerd in een fantoom studie.
De weefselfantomen zijn gemaakt van agar-agar met toegevoegde stoffen, waardoor de
akoestische eigenschappen kunnen worden gevarieerd. De akoestische eigenschappen
worden zó gekozen dat deze overeenkomen met die van biologische weefsels. De
geometrie van weefselfantomen is bekend.
De spatiële resolutie voor de tornogrammen van de geluidsnelheid, de
dempingscoëfficiënt en de dempingshelling is 1,0 - 1,5 mm. De spatiële resolutie in de
tornogrammen van de reflektiviteit is veel slechter. Strukturen kleiner dan 6.0 mm worden
niet zichtbaar.
De experimenteel bepaalde spatiële resolutie is afhankelijk van het contrast tussen het
detail en de omgeving. De relatie tussen de grootte van de zichtbare details en het contrast
is voor de gebruikte opstelling vastgelegd in contrast-detail diagrammen.
De kwantitatieve nauwkeurigheid is bepaald door de waarde van de akoestische
eigenschappen gemeten met de ultrasone tomograaf, te vergelijken met die bepaald met
een direkte meetmethode: ultrasone macroscopie. De resultaten van de kwantitatieve
vergelijking zijn uitstekend. Dit geeft aan dat een betrouwbare meting van de akoestische
eigenschappen van een voorwerp met behulp van ultrasone tomografie mogelijk is.
Uit een afzonderlijk experiment blijkt dat voor strukturen kleiner dan 10 mm een
afwijking van de werkelijke waarde optreedt. Dit wordt veroorzaakt door het spatiële laag-
doorlaat karakter van de meting en de reconstructie.
Belangrijk voor de beeldkwaliteit zijn de artefacten die worden veroorzaakt door
refraktie, interferentie en 'phase cancellation'. De effecten van deze verstorende
invloeden zijn in een fantoomstudie gei1lustreerd. De geluidsnelheid tornogrammen worden
het minst verstoord. De tornogrammen van de dempingscoëfficiënt en de dempingshelling
kunnen zodanig verstoord worden, dat de geometrie van de gebruikte weefselfantomen niet
meer te herkennen is.
De effecten van interferentie en 'phase cancellation' op de amplitude meting en de
meting van de verschuiving van de centrum frekwentie, zoals in een computersimulatie
voorspeld, worden experimenteel bevestigd.
Een bruikbare en effektieve correctiemethode is tot n?g toe niet gevonden. In de
literatuur voorgestelde oplossingen hebben slechts een marginaal effect of zijn praktisch
niet erg bruikbaar.

Hoofdstuk V

In hoofdstuk V worden metingen besproken aan weefsels die bot bevatten en aan
botweefsel zelf. Omdat de opstelling minder geschikt is voor het doen van in-vivo
metingen, betreft het voornamelijk in-vitro metingen.
Het eerste probleem waarop dit hoofdstuk zich concentreert, is de vraag of zachte
weefsels kunnen worden afgebeeld, als er ook botten in het scanvlak aanwezig zijn. Voor
deze metingen is gebruik gemaakt van een botfantoom gemaakt van Perspex en glycerine
dat in een weefselfantoom was aangebracht. Kwantitatieve analyse van de tornogrammen
toont dat de geluidsnelheid een betrouwbare afbeelding geeft. De dempingscoëfficiënt in

130
het zachte weefsel simulerende materiaal komt ook over een met de referentie waarde. De
dempingscoëfficiënt in het bot simulerende materiaal heeft geen overeenkomst met de
referentie waarde. De dempingshelling geeft een onbetrouwbaar kwantitatief resultaat.
Een belangrijk gezondheidsprobleem is de diagnose van botontkalking (osteoporose).
Vroegtijdige diagnose maakt het rnagelijk osteoporose tegen te gaan of te behandelen.
Ultrageluid lijkt potentieel een goede kandidaat om diagnostisch te gebruiken. Ultrasone
tomografie heeft zijn beperkingen in de te bereiken lichaamsdelen. Toch zou ultrasone
tomografie klinisch relevant kunnen zijn voor het meten van ontkalking van de botten in
de extremiteiten.
De mogelijkheid om botweefsel te meten wordt aan de hand van in-vitro metingen aan
een femur van een konijn gei11ustreerd. Het bleek alleen mogelijk om een consistente
verzameling projecties voor de dempingscoëfficiënt te meten. Reconstructie van
tornogrammen voor de geluidsnelheid en de dempingshelling was niet mogelijk.
Tot slot worden resultaten van enkele in-vivo metingen aan een vinger, een arm en een
been van een proefpersoon gepresenteerd.

Hoofdstuk VI

Het laatste hoofdstuk geeft een beschouwing van de ldinische perspektieven voor
ultrasone tomografie. Het uiteindelijke doel van alle onderzoek aan ultrasone tomografie
is de ontwikkeling van een techniek voor kwantitatieve weefselkarakterisering. Essentieel
hiervoor is dat diverse weefseltypen of toestanden van een weefsel door de akoestische
eigenschappen worden gekenmerkt.
Allereerst wordt er kort ingegaan op patroonherkenning. Hiermee worden methoden
aangeduid die gemeten kenmerken groeperen in klassen. De vier kenmerken die met de
beschreven ultrasone tornograaf worden gemeten zijn geluidsnelheid, dempingscoëfficiënt,
dempingshelling en de reflektiviteit. Niet altijd zijn alle kenmerken discriminerend tussen
de verschillende klassen. Voorafgaand aan klassificatie wordt er een reductie van de
kenmerken toegepast. Een gebrek aan consistente gegevens over de akoestische
eigenschappen van weefsels en de verstoring van de kwaliteit van de gemeten
tornogrammen maken verder onderzoek noodzakelijk, voordat met succes
patroonherkennende technieken in combinatie met ultrasone tomografie kunnen worden
toegepast.
De eerste klinische toepassing waarvoor ultrasone tomografie was bedoeld is de detectie
en diagnose van borstkanker. Deze toepassing voldoet aan de beperkende voorwaarden
dat het te onderzoeken lichaamsdeel rondom toegankelijk moet zijn en het geen gas mag
bevatten. Uit de gegevens beschikbaar in de literatuur wordt geconcludeerd dat ultrasone
tomografie momenteel niet concurrerend wordt geacht met de bestaande röntgen
mammografie gecombineerd met B-mode echografie. De door artefacten beperkte kwaliteit
van de tornogrammen en de geringe specificiteit van de akoestische waarden van
borstweefsels zijn hier debet aan.
Een andere mogelijke toepassing is de diagnose van botontkalking. Onderzoek naar
het gebruik van ultrageluid voor de diagnose van botontkalking is bekend uit de literatuur.

131
Over het gebruik van ultrasone tomografie hiervoor is nooit eerder gepubliceerd. In deze
studie zijn metingen uitgevoerd aan een bot van een konijn in-vitro en aan een vinger, een
arm en een been van een proefpersoon in-vivo. De resultaten tonen aan dat het gebruik van
ultrasone tomografie in relatie met botontkalking niet overschat moet worden.
Er worden enige aanbevelingen gedaan die volgen uit het werk dat in deze dissertatie
is beschreven en uit de huidige kennis over ultrasone tomografie in het algemeen. Voor
verder onderzoek is het hebben van een duidelijke klinische vraagstelling noodzakelijk.
Hiervoor kan een hierop toegespitst systeem worden herontworpen, waarmee dan een
klinische evaluatie kan worden uitgevoerd. Het systeem moet snel en eenvoudig in het
gebruik zijn.
In de algemene conclusie wordt tot slot gesteld dat met het prototype ultrasone
tornograaf vier akoestische parameters simultaan kunnen worden gemeten. De resultaten
worden verstoord door refraktie en interferentie van het geluid. De techniek wordt onder
andere hierdoor nog niet klinisch toegepast.

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Nawoord

Dit proefschrift beschrijft het onderzoek dat is verricht op de vakgroep Medische

Elektrotechniek van de Technische Universiteit Eindhoven, van maart 1989 tot en met
maart 1993, op het gebied van ultrasone tomografie en de mogelijke toepassing hiervan
voor kwantitatieve weefselkarakterisering.
Voor de totstandkoming van dit proefschrift wil ik iedereen die op de één of andere
wijze heeft bijgedragen, hartelijk bedanken.
In de eerste plaats geldt dit voor mijn familie, vrienden en collega's, die de afgelopen
jaren interesse hebben getoond in de voortgang van mijn onderzoek. De gesprekken en
jullie begrip gedurende de afgelopen jaren, heb ik zeer gewaardeerd en hebben mij altijd
gemotiveerd.
Thijs Stapper wil ik bedanken voor de tijd die hij altijd heeft genomen om te praten
over mijn ideeën en de problemen bij het onderzoek en het schrijven van dit proefschrift.
Professor Beneken, voor de grondigheid waarmee hij het proefschrift van commentaar
heeft voorzien. Door mijn nieuwe werkkring zullen we in de toekomst nog regelmatig over
gezamenlijke interesses kunnen praten.
Professor Bom, voor zijn bereidheid om voor de tweede maal als tweede promotor op
te treden bij een promotie over ultrasone tomografie in Eindhoven.
Professor Thijssen, voor zijn bereidheid om als co-promotor bij te dragen aan het
onderzoek en de leerzame gesprekken die we hebben gehad. Ook kreeg ik de mogelijkheid
om met Ton van der Steen enkele metingen uit te voeren met zijn opstelling op het
Biofysisch Laboratorium van het Academisch Ziekenhuis Nijmegen, afdeling
Oogheelkunde. Ton, bedankt!
Geert van den Boomen en Hennie van der Zanden, voor de kundigheid waarmee
elektrotechnische problemen werden opgelost en voor de figuren uit dit proefschrift die
Geert heeft verzorgd.
Tot slot wil ik Lieneke bedanken voor haar steun en voor de vanzelfsprekendheid
waarmee zij accepteerde dat ik zo nu en dan mijn prioriteiten moest omkeren. Zij
verzorgde de gezelligheid thuis en onderhield onze sociale contacten die ik het laatste jaar
enigszins verwaarloosde.

133
CURRICULUM VITAE

Jan Rietsema werd geboren in Zwolle in 1964. In juni 1992 is hij getrouwd met Lieneke
de Jong. Zij wonen in Eindhoven. Het VWO diploma behaalde hij aan de Rijks
Scholengemeenschap 'Hamaland' in Winterswijk. Hierna studeerde hij van september 1983
tot februari 1989 experimentele natuurkunde aan de Rijksuniversiteit Groningen. Zijn
afstudeeronderzoek heeft hij verricht aan het Interuniversitair Oogheelkundig Instituut in
Amsterdam bij de groep Visuele Systeem Analyse, onder supervisie van Prof. dr. ir. H.
Spekreyse. Het onderzoek betrof de lateralisatie van de corticale activiteit. Het
afstudeerwerk is nog enige tijd voortgezet door middel van een student-assistentschap. In
Groningen heeft de auteur in het bestuur van de Algemene Groninger Studenten
Roeivereniging 'Gyas' de verantwoordelijkheid gehad over de bouw van een nieuw
botenhuis, nadat het oude was afgebrand.
In de periode van maart 1989 tot maart 1993 is er onderzoek verricht op grond waarvan
dit proefschrift tot stand is gekomen. Het beschrijft een onderzoek naar ultrasone
tomografie. Dit werk is gedaan op de vakgroep Medische Elektrotechniek van de
Technische Universiteit Eindhoven, waar de auteur een aanstelling had als assistent in
opleiding (AiO). Gedurende deze periode was de auteur actief in het Landelijk AiO
Overleg en heeft geprobeerd constructieve bijdragen te leveren aan een goede
implementatie van het AiO-stelsel, en een serieuse behandeling van de AiO's als
beginnend wetenschappelijk onderzoekers.
Na de promotie zal hij gaan werken als universitair docent aan de Technische
Universiteit Eindhoven bij het TUE-Centrum Biomedische en Gezondheidstechnologie
binnen het project 'Gerontechnologie'. Gerontechnologie omvat het onderzoek naar een
optimale leef-, werk- en woonomgeving en aangepaste medische zorg voor ouderen, op
basis van de kennis van verouderingsprocessen.

134
 Stellingen

behorende bij het proefschrift

Assessment of ultrasound tomography

as a technique for
quantitative tissue characterization

door
Jan Rietsema

1. In ultrasone tomografie zijn verschillen in akoestische eigenschappen

een paradoxie. Het voor de meting benodigde contrast is tevens de
oorzaak van de verstoring van deze meting.
(dit proefschrift)

2. Het gebruik van de fast Hartley transformatie in beeldreconstructie

biedt voordelen ten opzichte van het gebruik van de reële fast Fourier
transformatie. Ten eerste gebruikt het algoritme minder rekentijd en ten
tweede is het van een veel grotere elegantie.
(R.N. Bracewell, IEEE ASSP 38, 1990, 2174-2176; dit proefschrift)

3. Behalve een implementatie van ultrasone transmissie tomografie is het

ook goed mogelijk ultrasone reflectie tomografie te implementeren
zonder het RF-signaal te digitaliseren.
(G. Sollie, Ultrasound transmission tomography: A low cost realization, 1988; dit
proefschrift)

4. Een klinische toepassing van ultrasone tomografie gebaseerd op de

rechte lijn voortplanting behoort, door fysische fenomenen inherent aan
de methode, vooralsnog niet tot de mogelijkheden.
(dit proefschrift)

5. De ontwikkeling van reconstructie algoritmen die rekening houden met

het refractie effect, zijn een essentiële stap voor een klinische
toepassing van ultrasone tomografie.
6. Indien medisch fysisch en medisch technisch onderzoek 'ab initio' van
een klinische vraag is voorzien, heeft het een veel grotere kans op
toepasbaarheid dan indien dit niet het geval is.

7. Opdat ouderen in belangrijke mate onafhankelijk kunnen blijven

functioneren en maatschappelijk aktief kunnen blijven, is er een
veranderende maatschappelijke attitude jegens hen nodig, naast het
aanbieden van leef-, werk- en woonomgevingen die ondersteunend zijn
bij hun dagelijkse aktiviteiten.
(Gerontechnology, International congress on technology and aging, Eindhoven,
augustus 1991)

8. De maatschappelijke opvatting over leiding geven vraagt een sociaal

vaardige, flexibele, creatieve en teamgerichte houding en een openstaan
voor andere culturen. De kwalifikatie 'vrouwelijk' voor deze
kwaliteiten is misleidend: er bestaan geen verschillen in stijl van
leidinggeven tussen vrouwen en mannen.
(Vrouwen, leiderschap en management. Onder red. van: M.l. Vemenint en
C.E. Disselen. Utrecht: Lemma, 1992)

9. Onderzoekscholen kunnen bijdragen aan een betere implementatie van

het AiO-stelsel en aan een grotere tevredenheid onder AiO's over dit
stelsel, indien er bij de opbouw van het curriculum serieus geluisterd
wordt naar de AiO's verbonden aan de onderzoekschooL
(Vorsers geven vorm: Reaktie op het regeringsstandpunt OnderzoekschooL
J. Rietsema, Eindhoven: LA/00, 1991; De opleiding van onderzoekers: Een evaluatie
naar hetfunctioneren van het AiO-stelsel. J.F.M.J. van Hout et al., Nijmegen: IOWO,
1992)

10. Een 'bijklussende hoogleraar' is als een dope gebruikende wielrenner:

het mogelijke voordeel voor de ploeg weegt niet altijd op tegen de
schadelijke bijwerkingen.
(de Volkskrant, december 1992)

11. Eén dag vakantie is vaak produktiever dan vele overuren.

Eindhoven, 9 juli 1993